AU2021241498B2

AU2021241498B2 - Methods of preventing and treating COVID-19 infection

Info

Publication number: AU2021241498B2
Application number: AU2021241498A
Authority: AU
Inventors: Sabine HAZAN
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-03-23
Filing date: 2021-03-22
Publication date: 2024-08-01
Anticipated expiration: 2041-03-22
Also published as: AU2024227651A1; AU2021241498A1; WO2021194970A1; CA3175350A1

Abstract

A method of preventing COVID-19 infection comprising the steps of: administering hydroxychloroquine; vitamin C; vitamin D; and zinc; and monitoring the individuals condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19. A method of treating an individual infected with COVID-19 comprising the steps of: administering hydroxychloroquine; azithromycin; vitamin C; vitamin D; and zinc; and monitoring the individual's condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19. The methods can further comprise administering ivermectin in and optionally doxycycline.

Description

METHODS OF PREVENTING AND TREATING COVID-19 INFECTION

CROSS REFERENCE TO RELATED APPLICATIONS

[00011 This application claims priority to United States Non-Provisional Patent

Application No. 17/114,271, titled "Method of Preventing COVID-19 Infection," filed

December 7, 2020, United States Non-Provisional Patent Application No. 16/953,674, titled

"Method of Preventing and Treating COVID-19 Infection," filed November 20. 2020, United

States Provisional Patent Application No. 63/110,877, titled "Methods of Preventing COVID

19 Infection with Ivermectin," filed November 6, 2020, United States Non-Provisional Patent

Application No. 17/026,051, titled "Methods of Preventing and Treating COVID-19

Infection," filed September 18, 2020, United States Provisional Patent Application No.

63/022,371, titled "Method of Treating and Preventing COVID-19 Infection," filed May 8,

2020, United States Provisional Patent Application No. 63/022,368, titled "Method ofUsing

Vitamin C, Vitamin D. Zinc, and Optionally Hydroxychloroquine, to Prevent COVID-19

Infection," filed May 8, 2020 United States Provisional Patent Application No. 63/002,494,

titled "Methodof UsingVitaminC,VitaminD Zinc, and Optionally Hydroxychloroquine, to

Prevent COVID-19 Infection," filed March 31, 2020, United States Provisional Patent

Application No. 63/001,161, titled "Method of Using Aerosolized Hydroxychloroquine,

Vitamin C, aid Zinc to Treat Covid-19 Infection," filed March 27, 2020 United States

Provisional Patent Application No. 62/993,345, titled "Method of Treating and Preventing

COVID-19 Infection," filed March 23, 2020, United States Provisional Patent Application

No. 62/993,159, titled "Method of Treating COVID-19 Infection with Antimicrobials," filed

March 23, 2020, andLnited States Provisional Patent Application No. 62/993,370, titled

"Method of Treating COVID-19 Infection with Antimicrobials," filed March 23, 2020, the

contents of which are incorporated by reference in theirentirety.

I BACKGROUND

100021 COVID-19 is a novel betacoronavirus that originated in bats in the city of

Wuhan, China. This disease has rapidly spread to become a worldwide pandemic, as

declared by the World Health Organization (WHO). Symptoms of COVID-19, including

fever, myalgia, coughing and shortness of breath, may appear from 2 and 14 days after

exposure. Approximately 20% of patients progress to severe illness, includingpneumonia,

respiratory distress, and even death. Cases in the UShaveincreasedfive-foldoverthelast

week, alone. The disease is spreading rapidly, arid a cure is desperately needed.

[00031 Nucleotide analogues, protease inhibitors and altered cellular bonding due to pH

change will maximize host protection by: optimizing levels of gamma interferon and

reducing the level of pathogenic microbes in the airways, especially in 'at risk' patients.

[00041 It is known that single anti-viral agents work poorly 'hen used alone in other

chronic viral infections such as Hepatitis C or HIV infection. Therefore, the greater the

number of anti-viral agents used in combination, the greater the cure rate.

[00051 Thus, there is a significant unmet need for preventing and treating this viral

infection. The present invention addresses this need.

SUMMARY

[00061 In a first embodiment, the invention herein is directed to my method of

preventing COVID-19 infection in an individual. The method of prevention comprises the

steps of providing an individual that is not infected with COVID-19; administering four

antimicrobials to the individual, wherein the antimicrobials comprise: chloroquine or

hydroxychloroquine: vitamin C; vitamin D; and zinc; and monitoring the individual's

condition over a pre-determined amount of time to determine the individual does not become

infected with COVID-19.

[00071 Optionally, the method of prevention comprises administering

hydroxychloroquine in a daily dosage range of 20 mg to 2,000 mg; administering vitamin C

in a daily dosage range of 250 mg to 10,000 mg; administering vitamin D in a daily dosage

range of 1,000 IU to 100,000 U; and administering zinc in a daily dosage range of 5 mg to

100 mg.

100081 Optionally, the method of prevention comprises administering, on day 1: 400 mg

of hydroxychloroquine; 3,000 mg of vitamin C; 3,00 IU of vitamin D; and 50 mg of zinc;

and administering on day 2: 3,000 mg of vitamin C;3,000 IU of vitamin D; and 50 mg of

zinc.

100091 Optionally, the method of prevention comprises administering ivermectin in a

daily dosage range of 12 mg to 18 mg and, optionally administering doxycycline in a daily

dosage amount of 400 mg.

[00101 In a second embodiment, the invention herein is directed to my method of

treating an individual infected with COVID-19. The method of treatment comprises the steps

of providing an individual infected with COVID-19; administering five antimicrobials to the

individual, wherein the antimicrobials comprise: chloroquine or hydroxychloroquine;

azithromycin; vitamin C; vitamin D; and zinc; and monitoring the individuals condition over

a pre-determined period of time to determine whether the individual is no longer infected

with COVID-19.

100111 Optionally, the method of treatment comprises administering hydroxychloroquine

in daily dosage range of 20 g to 2,000 mg; administering azithromycinin a daily dosage

range of 250 mg to 500 mg; administering vitamin C in a daily dosage range of 250 mg to

10.000 tg; administering vitamin D in a daily dosage range of 1,000 LU to 100,000 IU; and

administering zinc in a daily dosage range of 5 mg to 100 mg.

3t

[00121 Optionally, the method of treatment comprises the steps of administering, on day

1: 400 mg of hdroxychloroquine; 500 mg of azithromycin; 3,000 mg of vitamin C; 3,0001I

of vitanuin D; and 50 mug of zinc; administering daily, on days 2 to 400 mug of

hydroxychloroquine; 250 mg of azithromycin; 3,000 mg of vitamin C;3,000 1U of vitamin D;

and50 mg of zinc; and administering daily, on days 6 to 10: 400 mg of hydroxychloroquine;

3,000 mg of vitamin C;3,000 LU of vitaim D; and 50 mg of zinc.

[00131 The method of treatment can further comprise administering daily, on days 6 to

10, administering 250 mg of azithromycin.

[00141 Optionally, the method of treatment comprises administering ivermectin in a

daily dosage range of 12 mg to 18 mg and, optionally, administering doxycycline in a daily

dosage amount of 400 mg.

BRIEF DESCRIPTION OF THE DRAWINGS

[00151 Further advantages of the present invention may become apparent to those skilled

in the art with the benefit of the following detailed description of the preferred embodiments

and upon reference to the accompanying drawings in which:

[00161 FIG. 1 is a flow chart depicting the steps of a first method of preventing infection

of an individual with COVID-19;

[00171 FIG. 2 is a flow chart depicting the steps of a second method of preventing

infection of an individual with COVID-19;

[00181 FIG. 3 is a flow chart depicting the steps of a first method of treating an

individual infected with COVID-19

[00191 FIG. 4 is a flow chart depicting the steps of a second method of treating an

individual infected with COVID-19;

[00201 FIG. 5A is a graphical representation of whole genome alignment of SARS-CoV

2 in patient I of Example 6;

[00211 FIG. 5B is a graphical representation of whole genome alignment of SARS-CoV

2 in patient 3 of Example 6

[00221 FIG. 5C is a graphical representation of whole genome alignment of SARS-CoV

2 in patient 4 of Example 6

[00231 FIG. 5D is a graphical representation of whole genome aligninent of SARS-CoV

2 in patient 6 of Example 6;

100241 FIG. 5E is a graphical representation of whole genome alignment of SARS-CoV

2 in patient 8 of Example 6;

100251 FIG. 5F is a graphical representation of whole genome alignment of SARS-CoV

2 in patient 10 of Example 6;

100261 FIG. 5G is a graphical representation of whole genorne alignment of SARS-CoV

2 in patient 11 of Example 6: and

100271 FIG. 5H is a graphical representation of whole genome alignment of SARS

CoV-2 in patient 12 of Example 6.

DETAILED DESCRIPTION

100281 As used herein, the following terms and variations thereof have the meanings

given below, unless a different meaning is clearly intended by the context in which such term

is used.

[00291 The terms "a," "an," and "the" and similar referents used herein are to be

construed to cover both the singular and the plural unless their usage in context indicates

otherwise.

100301 As used in this disclosure, the term "comprise" and variations of the term, such

as "comprising" and "comprises," are not intended to exclude other additives, components,

integers ingredients or steps.

[00311 Referring now to the drawings, wherein like reference numerals designate

identical or corresponding features throughout the several views. Further, described herein

are certain non-limiting embodiments of ny pipeline filter assembly for pool filtering and

maintenance.

[00321 The following discussion describes in detail multiple embodiments of the

invention with several variations of those embodiments. This discussion should not be

construed. however, as limiting the invention to those particular embodiments. Practitioners

skilled in the art will recognize numerous other embodiments as well.

[00331 In a first embodiment, the present invention is directed to a first method of

preventing COVID-19 infection in an individual. The method involves administration of

chloroquine or hydroxychloroquine, Vitamin C, Vitamin D, and Zinc. Both methods are

discussed in greater detail below.

[00341 Referring now to Figure 1, there is shown the first method of prevention. The

method of prevention comprises administering four different antimicrobials. The four

antimicrobials comprise: chloroquine or hydroxychloroquine, vitamin C, vitamin D, and zinc.

100351 Day I the individual takes the following, ideal, regimen outlined in Table 1:

Drug AM Dose PM Dose

Hydroxychloroquine 200mg 200mg

Vitamin C 3000mg

Vitamin D 30001U

Zinc 50mg

Table 1

[00361 Optionally, the method of prevention can comprise administering on day 2: 3,000

mg of vitamin C; 3,000 I of vitamin D; and 50 mg of zinc.

[00371 Hydroxychloroquine is administered only on day 1. The half-life of

hydroxychloroquine is up to 32 days, thus treatment with this drug for one day should be

sufficient. However, should the need to prevent the infection or disease last longer than 32

days, repeat dosing can be considered. Accordingly, if necessary, the cycle of day I followed

by day 2 can be repeated weekly, every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7

weeks, or 8 weeks.

[00381 Vitamin C is administered at 3,000 mg per day ongoing. This 3,000 mg can be

broken up into two 1500 mg doses, one taken in the morning and one taken atnight.

[00391 Vitamin D is administered at 3,000 IU per day ongoing. This 3,000 U can be

broken up into two 1500 IU doses, one taken in the moving and one taken at night.

[00401 Zinc is administered at 50 mg per day ongoing. This 50 mg can be broken up into

two 25 mg doses, one taken in the morning and one taken at night.

[00411 Chloroquine or hydroxychloroquine can be administered in a daily dosage range

of 20 mg to 2,000 ig. The above amounts recited in the tables are notlimiting.

[00421 Vitamin C can be administered in a daily dosage range of 250mg to10000mg.

The above amounts recited in the tables are notlimiting.

[00431 Vitamin D can be administered in a daily dosage rage of 1,000 IU to 100,000 IU.

The above amounts recited in the tables are not limiting.

[00441 Zinc can be administered in a daily dosage of 5 mg to 100 mg. The amount of

Zinc can be reduced to 25 igper day if gastrointestinal upset occurs,

[00451 Zinc, Vitamin C and D help in numerous aspects of viral protection through

cellular metabolism, including catalytic activity of enzymes, and play roles in immune

function, protein synthesis.

[00461 The chloroquine or hydroxychloroquine can come in various forms: as a pill,

liquid solution, lozenges, topical treatment such as a cream or oil, or any other means of

delivery. Hydroxychloroquine prevents cytokine release, and cytokine release is what causes

anaphylactic flush. Optionally, the hydroxychloroquine is sprayed directly on the users

tongue.

100471 In a second embodiment, the present invention is directed to a second method of

prevention that comprises administering three different supplements comprising vitamin C,

vitamin D, and zinc, and mixtures thereof, to an individual.

[00481 Referring now to Figure 2, there is shown the second method of prevention. The

length of preventative treatment of the present invention can be as long asnecessary.

However, regardless of the length of treatment, Vitamin C is provided at 10,000mg daily for the first three days of treatment, and then 3000mg daily thereafter. This 10,000 mg of

Vitamin C can be broken up into two doses, one taken in the morning and one taken at night.

[00491 Vitamin D is provided at 40,000 IU one day every 4weeks (or however many

weeks the preventative treatment lasts). This 40.000 IU of Vitamin D can be broken up into

two doses, one taken in the morning and one taken at night.

00501 Zineisprovidedat50mgperdayongoing, for the length of the preventative

treatment. This 50 mg of Zinc can be broken up into two doses, one taken in the morning and

one taken at night.

[00511 On Day I (Week 1), the patient provides verbal informed consent, the patient

reviews prior (previous 3 months) and concomitant medications and the patient receives the

three different supplements: Vitamin C, Vitamin D, and Zinc. The patient takes 10,000 mg of

Vitamin C, 40,000 IU of Vitamin D, and 50 mg of zinc.

[00521 On Days 2 and 3 (Week 1), the patient takes 10,000 mg of Vitamin C and 50 mg

of zinc daily. This 3,000 mg can be broken up into two 1500 mg doses, one taken in the

morning and one taken at night, The patient is called on the phone for assessment for

potential adverse events (AE) and serious adverse events (SAE), and any COVID-19

symptoms.

[00531 On Days 4-7 (Week 1), the patient takes 3,000 mg of Vitamin C and 50 mg of

zinc daily.

[00541 On Day 8 (Week 2), the patient takes 3,000 mg of Vitamin C, 40,000 IU of

Vitamin D, and 50 mg of zinc.

[00551 On Days 9-14 (Week 2), the patient takes 3,000 mg of Vitamin C and 50 mg of

zinc daily.

[00561 Weeks 3-24 continue with the same protocol identified above for Week 2.

[00571 Treatment can be for one day or consecutive or repeated in 2 weeks, 1 month, 6

months or 1 year.

[00581 Optionally, Vitamin C dosage can range from 1000mg to 10,000mg per day,

Vitamin D dosage can range from 1000 IU to 40000 IU per day, Zinc (the zine can be any

type or form of zinc) dosage can range from 25-75 ig per day. As noted above, all daily

doses of Vitamin C, Vitamin D and Zinc can be broken up into two daily doses, wherein one

dose is taken in the morning and one dose is taken in the evening. For all protocols provided

in this application, when a dosage range is provided, any dosage amount that is included in

that range can be administered, Accordingly, the invention is not limited to the dosage ranges

disclosed, and includes all dosage amountscontained in those ranges.

[00591 The protocols provided in this application can also include selenium, copper and

other vitamins that are deemed appropriate supplements for Vitamin C, Vitamin D or Zinc or,

to counteract the negative depletion of certain vitamins, like copper or selenium.

[00601 The Vitamin C, Vitamin D and Zinc, and mixtures thereof, can be administered

orally, in the form pills/lozenges, an aerosolized spray, or a food substance such as a liquid

drink or yogurt composition. Optionally, the Vitamin C. Vitamin D and Zinc can be

administered in the formof a nasal spray or a topical application, such a lotion or spray for

administration on the individual's skin.

100611 In the methods of prevention described above, all, or any combination of, the

antimicrobials/suppements disclosed above can be administered in the form of a single small

atomizer. The patient sprays the atomizer towards the back of their throat. The spray is

administered at least once a day but preferably twice a day when coughing starts. Use of the

atomizer continues as directed by the supervising physician.

[00621 In a second embodiment, the present invention is directed to a first method of

treating an individual with infection or disease with five different antimicrobials. The five antimicrobials comprise: hydroxychloroquine, azithromycin, vitamin C, vitamin D and zinc.

Referring now to Figure 3. there is shown the first method of treatment.

[00631 Day I following positive test (isolation), the individual takes the following

regimen outlined in Table 2:

Drug AM Dose PM Dose

Hydroxychloroquine 200mg 200mg

Azithronvcin 500mg

Vitamin C 3000mg

VitaminD 30001U

Zinc 50mg

Table 2

[00641 On Day 2-Day 5 the individual takes the following regimen outlined inTable 3:

Drug AM Dose PM Dose

Hydroxychloroquine 200mg 200mg

Azithromycin 250mg

Vitamin C 3000ing

VitaminD 30001U

Zinc 50mg

Table 3

100651 On Day 6-Day 10, the individual takes the following regimen outlined inTable 4:

Drug AM Dose PM Dose

Hydroxychloroquine 200mg 200rn

Vitamin C 3000mg

VitaminD 3000iU

Zinc 50mg

Table 4

100661 Hydroxychloroquine is administered daily, at 200 mg twice daily for days 1-10.

[00671 Azithromycin is administered daily, at 500 mg on day 1, and 250 mg days 2-5.

Optionally, azithromycin can be administered at 250 mg per day for 5-10 days with a loading

dose of 500 mg x day 1 or simply 250mg on day 1. Azithromycin may be substituted with

doxycycline at a daily dosage range of 25 mg to 800 nig, for those unable to take

azithromycin. Alternatively, nocycline or antibiotics that inhibitbacterialS ribosomal

RNA, and mixtures thereof, may be used.

[00681 Optionally, natural products like quercetin and artemesia, and mixtures thereof

may be used, as well as any natural compounds that are used to make hydroxychloroquine or

azithromycin, and mixtures thereof Accordingly, any mixture of any of the above recited

compositions may be used.

[00691 Vitamin C is administered at 3,000 mg per day ongoing. This 3,000 mg can be

broken up into two 1500 mg doses, one taken in the morningand one taken at night.

[00701 Vitamin D is administered at 3,000 IU per day ongoing. This 3,000 IL can be

broken up into two 1500 IU doses, one taken in the morning and one taken at night.

[00711 Zinc is administered at 50 mg per day ongoing. This 50 mg can be broken up into

two25 mg doses, one taken in the morning and one taken at night.

[00721 Chloroquine or hydroxychloroquine can be administered in a daily dosage range

of 20 mg to 2,000 mg. The above amounts recited in the tables are not limiting. The chloroquine or hydroxychloroquine can come in various forms: as a pill, liquid solution, lozenges, topical treatment such as a cream or oil, or any other means of delivery.

Hydroxychloroquine prevents cytokine release, and cytokine release is what causes

tongue.

100731 Vitamin C can be administered in a daily dosage range of250 mg to 10,000mg.

The above amounts recited in the tables are notlimiting.

100741 Vitamin D can be administered in a daily dosage rage of 1,000 IU to 100,000 IU.

The above amounts recited in the tables are notlimiting.

[00751 Zinc can be administered in a daily dosage of 5 mg to 100 mg. The amount of

Zinc can be reduced to 25 mg per day if gastrointestinal upset occurs.

[00761 Concurrently with the above treatment, the individual is self-quarantined per CDC

recommendations.

100771 Optionally, for the method of treatment noted above, as the dosages of the

hydroxychloroquine, vitamin C, vitamin D and zinc remain the same throughout treatment;

all four of those antimicrobials can be administered in the form of a single small atomizer.

The patient sprays the atomizer towards the back of their throat. The spray is administered at

least once a day, but preferably tice a day when coughing starts. Use of the atomizer

continues as directed by the supervising physician.

[00781 For all protocols provided in this application, vitamin C dosage can range from

250 mg to 10,000 mg per day, vitamin D dosag can rangefrom1000I(mg)to100,000 IU

(mg) per day, zinc (which can be any form or type of zinc) dosage can range from 5 mg to

100 mg per day, and hydroxychloroquine dosage can range from 50 mg to 2,000 mg per day

for a treatment period of I to 10 days treatment. Optionally, hydroxychloroquine can be administered once as single dose. For all protocols provided in this application, when a dosage range is provided, any dosage amount that is included in that range can be administered. Accordingly, the invention is not limited to the dosage ranges disclosed, and includes all dosage amounts contained in those ranges.

[00791 Optionally, the above protocols can include selenium, copper and other vitanuns

that are deemed acceptable supplements for vitamin C, vitamin D or zinc or to counteract the

negative depletion of certain vitamins, which is why copper or selenium are typically used.

[00801 Treatment can be for one day or consecutive or repeated in 2 weeks, I month. 6

months or I year, or weekly for 6 months.

[00811 In a third embodiment, the present invention is directed to a second method of

treating COVID-19 infection. Referring now to Figure 4, there is shown the second method

of treatment.

[00821 The ivermectin can either be administered while the patient is undergoing the

first method of treatment discussed above, or after the patient has undergone 5 to 7 days of

the treatment of the method of treatment discussed above.

[00831 The dosage amount for the ivermectin is 12-18 mg/day The ivermectin can be

administered daily, for up to 10 consecutive days, or alternatively, the ivermectin can be

administered on day 1 day 3/day 4 and day 7/day 8 of a 10 day period. The 10 day period can

either be in conjunction with administration of the treatment of the first method of treatment

discussed above, or following the completion of the 5 to 7 days of treatment with the first

method of treatment discussed above.

[00841 Ivermectin can be administered in a pill/tablet, a nasal spray, an oral spray, or a

topical ointment.

[00851 Optionally, natural products as well as any natural compounds, and mixtures

thereof that are used to make ivermectin may be used as an alternative to ivermectin.

[00861 Optionally, either the first or the second methods of treating COVID-19 infection

can also include administering doxvcycline (or any other alternatives listed above and

mixtures thereof) to the patient in a dosage amount of 200 mg, by mouth, twice a day, for up

to 10 consecutive days.

[00871 Accordingly, combining the first and second methods of treatment discussed

above can result in a combined method of treatment that can include the use of

hydroxychloroquine, azithromycin, ivermectin, doxycycline, vitamin C, vitamin D and zinc,

taken all at the same time.

[00881 The above protocols can be used to prevent and treat other viruses (not just

COVID-19), including other flu and various respiratory viruses, including more benign

coronaviruses andtrhinoviruses.

[00891 The above protocols can also be used to prevent and treat Autism, Parkinson's,

Alzheimer's and otherneurological diseases.

[00901 EXAMPLES

[00911 Example 1: Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for Prevention

of COVID-19 Infection

[00921 Objective: To determine whether treatment with hydroxychloroquine, vitamin C,

vitamin D. and zinc in combination will prevent infection with COVID-19 and to assess the

safety and tolerability of hydroxychloroquine, vitamin C, vitamin D, and zinc in healthy,

high-risk individuals without hypertension, and no evidence of COVID-19 infection.

100931 Procedure: Dav 1: Prescription of study drugs and home health monitoring

equipment. The study drugs are hydroxychloroquine 200mg twice a day for I day only,

vitamin C 3000mg per day ongoing, vitamin D 3000mg per day ongoing. and zinc 50mg per

day ongoing per day. The home health monitoring equipment is an electrocardiogram (EKG)

which synchs up with a sniartphone

[00941 Days 2-7: Patient collects the EKG once during this week using the home health

equipment

[00951 Weeks 1-23: Patient provides an assessment of any COVID-19 symptoms and

continues to collect EKG weekly throughout the remainder of the trial

[00961 Week 24: Patient undergoes confirmatory COVID-19 testing which consists of

nasopharyngeal (NP) and oropharyngeal (OP) swabs collected according to CDC (Center for

Disease Control) protocol. The swabs consist of synthetic fiber swabs with plastic shafts. NP

swabs are collected by insertion of a swab into the nostril parallel to the palate. The swab is

left in place a few seconds to allow it to absorb secretions. OP swabs are inserted into the

oropharynx parallel to the palate, avoiding the tongue. The swab is left in place a few seconds

to allow it to absorb secretions. The swabs are thenimmediately placed in sterile tubes with

2-3nL of viral transport media. The tubes are placed in biohazard bags then boxes and

couriered to the local Public Health Lab.

[00971 Table 5 provides a schedule ofevents for Example 1.

Screening Weeks Week Assessment Day 3 (Day 1) 1-23 24

Informed consent and demographics X

Review of prior and concomitant medications X

EKG at home X X

Prescription of Hydroxychloroquine, vitamin C, vitamin X D and zinc

Provision of home health EKG and pulse oximeter X

Update list of prior and concomitant medications X X X

Ask about any adverse events and any serious adverse x x X events

Evaluation of COVID-19 symptoms X X

COVID-19 testing X

Blood draw forfuture testing X

Vitals in-clinic X

Physical exam X

Table 5

[00981 Regarding Table 5: Vitals at home to include EKG and O2Sat, future testing will

require separate informed consent and could possibly include antibody or cytokine testing,

and vitals in-clinic to include height, weight., blood pressure (following 5 minutes sitting)

pulse, respiratory rate, temperature, and oxygen saturation,

[00991 Example 2: Randomized, Double-Blind. Placebo-Controlled Phase IIA Study of

Hydroxychloroquine. Vitamin C, Vitamin D. and Zinc for the Prevention of COVID-19

Infection

[001001 Oebjenves.:_ Prevention of COVID-19, Lack of COVID-19 symptoms, and

assessment of safety and tolerability

[00101] Procedure: Screening Period (Days -5 to -1): Prescription of home health

monitoring equipment that includes a thermometer, a pregnancy test if applicable, and a daily

diary. There are twogroups being studied: Arm I and Arm 2.

[00102] Arm I is prescribed the following antimicrobials: hydroxychloroquine 200mg

twice a day for I day only, vitamin C 3000IU per day for 12 weeks, vitamin D 30001U per day for 12 weeks, and zinc 50mg per day for 12 weeks. The zinc can be reduced to 25 ng if

(I upset occurs.

[001031 Arm 2 is prescribed thefollowing antimicrobials:Placebo twice a day for 1 day

only, vitamin C30001Uper day for 12 weeks, vitamin D 30001U per day for 12 weeks, and

zinc 50mg per day for 12 weeks. The zinc can be reduced to 25 mg if(i upset occurs.

100104] Day 1: Patient is called to teach them how to use the diary in the EDC, discuss

the medication regimen, and answer any questions they may have. Patient takes pregancy

test if applicable, collects a temperature reading, completes their diary, and takes the

prescribed treatment regimen. Table 6 outlines the prescribed treatment regimen for Day 1.

Drug AM Dose PM Dose

Hvdroxychloroquine (or placebo) ~O ~~0m

Vitamin C 30ng

VitaminD 30001U

zinc Zie50mg

Table 6

[001051 Day 2: Patient collects a temperature reading, completes their diary, and is called

on the phone for assessment of any adverse events or serious adverse events, assessment of

any COVID-19 symptoms, the list of prior and concomitant medications is updated, any

questions the patient has are answered, and the patient takes their prescribed treatment

regimen. Table 7 outlines the prescribed treatment regimen for Day 2.

Drug AM Dose PM Dose

Vitamin C 3000mg

VitaminD 30001U

Zinc 50mg

Table 7

100106] Days 3-10: Patient collects a temperature reading, completes their diary, and

takes their prescribed treatment regimen. Table 8 outlines the prescribed treatment regimen

for Days 3-10.

Drug AMDose PM Dose

Vitamin C 3000mg

Vitamin D 3000IU

Zinc 50mg

Table 8

100107] Day 14: The patient is called for instruction on how to collect a nasal swab and

package for shipping, assessment COVID-19 symptoms, updating their list of prior and

concomitant medications, and answering any questions they may have.

[001081 Weeks 3-11: The patient is called weekly for assessment of any adverse events or

serious adverse events, assessment of any COVID-19 symptoms, updating their list of prior

and concomitant medications, and answering any questions they may have. The patient takes

weekly temperature readings, completes their diary, and takes the prescribed treatment

regimen. During Week 4 the patient is reminded to collect a nasal swab. The prescribed

treatment regimen for Weeks 3-11 is shown in Table 9.

Drug AM Dose PM Dose

Vitamin C 3000mg

Vitamin D 3000 IU

Zinc 50mg

Table 9

[00109] Week 12: The patient presents to the clinic for evaluation that includes

assessment for adverse events and serious adverse events, updating their list of prior and

concomitant medications, a physical exan nasal swab collection and COVID-19 sample

collection.

100110] Samples for COVID-19 testing are collected using synthetic swabs with plastic

shafts. Nasal swabs are collected and immediately placed into a sterile vial with 2-3 mL of

viral transport media. The vials are placed into biohazard bags, boxed up, the box sterilized,

and picked up for shipment to the central laboratory. Samples are tested byRT-PCR.

100111] Table 10 presents the schedule of events for Example 2.

Informed Consent & Demographics X Initial Review of Prior and Concomitant Medications X Medical Records review, including baseline EKG X Randomization X Prescription of Hydroxychloroquine or placebo, vitamin C, vitainin D, and zinc Provision of daily diary., thermometer and pregnancy X test Pregnancy Test if applicable X Temperature at home X X X X X X X X Complete daily diary X X X X X X X X Hydroxychloroquine 200mg X Vitamin C 3000mg XX X X X X X X Vitamin D 3000 IU X X X X X X X X Zinc 50mga X X X X X X X X Phone/video call to patient" X X X X X X X Update list of prior and concomitant medications X X X X X X X X Askabout AE and SAE X X X X X X X X Assessment of COVID-19 symptoms N X N N N N N X

Swabs for R:T-PCRXXX Vitals ini-clinic` X Phy sical Exami X

Table 10

[001121 Regarding Table 10: The Zinc may be reduced to 25rng if GI upset occurs,

phone/video calls to the patient occur weekly during Weeks 2-11, and vitals in-clinic include

height, weight, blood pressure (following 5rminutes sitting) pulse, respiratory rate,

temperature, and oxygen saturation.

[00113] Statistical Analysis: The treated patients in this study are compared to the

placebo group. Measurements include PCR test results, presence or absence of symptoms,

and symptom severity.

[00114] The change of these measurements from the end to the baseline (post-pre) are

used as the primary outcome, for example e = pel - eO, where pel and peO are the

outcome of patients from the treatment group at the end and at baseline, respectively.

100115] I A-0sa list.1< A> 0 where60 isaclinicallymeaningful threshold to measure the disease symptoms. In this study, that meaningful threshold is

calculated as mean change in clinical symptoms as recorded in the diary, from baseline

through week 12. Each category in the diary is assigned a number, 0 for None, I for Mild, 2

for Moderate and 3 for severe. Each category is analyzed independently and as a group.

100116] Categorical variables are summarized by presenting the number (n) and percent

(%)of subjects in each category. All Statistical tests for the analysis are performed using the

p<0.05 level of significance. All confidence intervals are one-sided.

[001171 Since these are healthcare workers who are exposed to COVID-19 at every shift,

efficacy is determined by RT-PCR testing, as well as the presence or absence of symptoms as

recorded in the patient diary via EDC.

[001181 Example 3: Use of Hydroxchloroquine, Azithromycin, Vitamin C, Vitamin D,

and Zinc to treat COVID-19 Infection (HAZDPAC)

[001191 Objectives: test the efficacy of hydroxychloroquine, azithromycin, vitamin C,

vitamin D, and zinc in the treatment of patients with COVID-19 infection and to assess the

safety and tolerability of this treatment in patients with COVID-19 infection.

100120] Procedure: First, the patient is determined to have COVID-19.

[001211 Day I following positive test (isolation): The patient takes prescribed regimen

outlined in Table 11.

Drug AM Dose PM Dose Hvdroxychloroquine 200mg 200mg Azithroniycin 500mg Vitamin C 3000mg Vitamin D 30001U Zinc 50mg - Table 11

[001221 Day2-Day 5: The patient takes the prescribed regimen outlined in Table 12.

.D ru, g _ _ _ _ _ _ _ _ _----------------A M D ose __ _ _ _PM _D ose ---------- Hydroxvchloroquine_____ 200mg _________200m-- Azithromvcin 250mg Vitamin C 3000mg_ - Vitamin D 3000IU Zinc 50mg Table 12

[00123] Day 6-Day10: The patient takes the prescribed regimen outlined in Table 13.

Drug AM Dose PM Dose Hydroxychloroquine _200ig 200mg Vitamin C 3000mg Vitamin D 3000IU Z inc -------------- m-------- -----------------------------

Table 13

100124] Follow-Up Period: Month I (outpatient only AFTER negative test): vital signs

are taken that include blood pressure, heart rate, respiratory rate, oxygen saturation, temperature), the patient is assessed for adverse events and serious adverse events, and swabs for PCR are taken.

[00125] Month 3 (outpatient): vital signs are taken that include blood pressure, heart rate,

respiratory rate, oxygen saturation, temperature), the patient is assessed for adverse events

and serious adverse events, and swabs for PCR are taken.

100126] Month 6 (outpatient) vital signs are taken that includes blood pressure, heart rate,

and serious adverse events, and swabs for PCR are taken.

[001271 Month 9 (outpatient) vital signs are taken that includes blood pressure, heart rate,

and serious adverse events, and swabs for PCR are taken,

[001281 Month 12 (outpatient) vital signs are taken that includes blood pressure, heart

rate, respiratory rate, oxygen saturation, temperature), the patient is assessed for adverse

events and serious adverse events, and swabs for PCR are taken.

[00129] COVID-19 sample collection procedure is as follows: nasopharyngeal (NP) and

oropharyngeal (OP) swabs are collected according to CDC protocol. The swabs comprise

synthetic fiber swabs with plastic shafts, NP swabs are collected by insertion of a swab into

the nostril parallel to the palate. The swab is left in place a few seconds to allow it to absorb

secretions. OP swabs are inserted into the oropharynx parallel to the palate, avoiding the

tongue. The swab is left in place a few seconds to allow it to absorb secretions. NP and OP

swabs are immediately placed in sterile tubes with 2-3mL of viral transport media. The tubes

are placed in biohazard bags then boxes and couriered to the local Public Health Lab. Table

14 outlines the schedule of events for Example 3.

Table 14

-0 4

+1 5+ +5 +5

Assessment 21 2 2 2 formed Consent & Demographics X Confirmation of Positive PCR for X COVID-19 Review of Medical Records x Vitals, X X X X X Prescription of Antimicrobialsb X Ask about AE and SAE x x x x X X

100130] Regarding Table 14: Vitals to include height (only at first visit), weight, blood

pressure(following5ninutessitting) pulse, respiratory rate, temperature, and oxygen

saturation. Dosage to be given as in section 8, below

[001311 Table 15 provides a summary of the antimicrobial dosage of Example 3.

Treatment Method Medication Dose Frequency Hydroxychoroquine 200mg BID AMIthomycin 500ng\IDayi1->250mg Day 2-5 Dailk Quintuple Therapy Vitamni(C 3000mg__ Dail Vitamin D 5000IU Daily Zinc 50mg Daily

Table 15

[001321 Exampie4:RandominzeDouble-BlindPlacebo-Controlled PhaselIAStudiof

HydroxchoouineAithoycin.itamin &Vitamin._andZinectotreatCOVID-19

Infection

100133] Objectives: Test the efficacy of hydroxychloroquine, azithromycin, vitamin C.

safety and tolerability of this treatment in patients with COVID-19 infection.

[001341 Procedure: First, the patient's diagnosis of COVID-19infection is confirmed.

[00135] Screening Period (Days -3 to -1): Prescription of home health monitoring

equipment that includes a thermometer, a pulse oximeter, a pregnancy test if applicable, and a

daily diary. There are two groups being studied: Arm 1 and Arm 2.

100136] Armi is prescribed the following antimicrobials: ydroxychloroquine 200MG

BID for 10 days; Azithromycin 500mg on day 1, 250mg day 2-5; Vitamin C 3000U for 10

days, then 1500mg for 20 days Vitamin D 30001U for 10 days, then 1500IU for 20 days

and Zinc 50mg for 10 days, then 25mo for 20 days.

[001371 Arm 2 is prescribed the following antimicrobials: Placebo for

Hydroxychloroquine BID for 10 days; Placebo for Azithromycin to be taken 2 the on Day 1,

then I on Days 2-5; Vitamin C 3000mg for 10 days, then 1500mg for 20 days; Vitamin D

3000IU for 10 days, then 15OOILfor 20 days; and Zinc 50mg for 10 days, then 25mg for 20

days. Table 16 outlines the prescribed antimicrobials discussed above.

Treatment Medication Dose Frequency

Method

Hydroxychloroquine 200mg BID

Azithromycin 500mg \Day 1->250mg Day 2-5 1Daily

Q uintuple ------------------------------------------------------------------- ----------------- -------------- Vitamin C 3000mg Daily Therapy Vitamin D 5000111 Daily

Zinc 50mg Daily

Placebo 1 tablet BID

Placebo 2 tablets day 1, then 1 tablet day Daily

2-5 Placebo Vitamin C 3000mg 1Daily

Vitamin D 3000lU Daily

Zinc 50mg Daily

Table 16

[00138] Treatment Period: Day 1 following positive test (isolation), the patient is video

called to ensure they have all study materials and the following is discussed: Use of home

health equipment, Subject will take baseline measurements at this time and record it in the

diary, Diary and how to transmit its contents, Medication dosing, Subject will take pregnancy

test if applicable, Subjecti use provided equipment to measure vital signs such as EKG,

Oxygen Saturation, and Temperature. The patient takes prescribed regimen outlined in Table

17.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 200mg 200mg

Azithromycin (or Placebo) 001g

3000rne Vitamin C

VitaminD D

Zinc 0mg

Table 17

[001391 Day 2: The patient completes theAM and PM diary entries, the patient uses the

provided equipment to measure vital signs such as EKG, Oxygen saturation., and temperature,

and the patient takes the prescribed regimen outlined in Table 18.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 200mg 200mg

Azithromycin (or Placebo) 250mg

Vitamin C 3000mg

Vitanin D 3000U

Zinc 50mg

Table 18

[001401 Day 3: The patient is called and asked if they are experiencing any difficulties

withswab collection, whether there have been any adverse events and/or serious adverse

events, the list of prior and concomitant medications is updated, the patient is asked about

symptom resolution or progression, the patient is instructed on how to collect nasal swabs,

and the patient then collects the first nasal swab. The patient completes their AM and PM

diary entries, and collects their vital signs such as EKG, oxygen saturation and temperature.

The patient takes the prescribed regimen outlined in'Table 19,

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 200mg 200mg

Azithromycin (or Placebo) 250mg

Vitamin C 000mg

Vitamin D 30001U

Zinc 50mg

Table 19

[001411 Day 4: The patient completes theirAM and PM diary entries, collects their vital

signs, and takes the prescribed regimen outlined in Table 20.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 200mg 2 2100mg

Azithromycin (or Placebo) 250mg

3000mgi Vitamin C

Vitamin D

Zinc 50mg

Table 20

[00142] Day 5: The patient completes their AM and PM diary entries collects their vital

signs, collects a nasal swab, and takes the prescribed regimen outlined in Table 21.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 200mg 200mg

Azithromycin (or Placebo) 250mg

Vitamin C 000mg

Vitamin D 30001U

Zinc 50mg

Table 1

100143] Day 6: The patient completes their AM and PM diary entries, collects their vital

signs, and takes the prescribed regimen outlined in Table 22.

Drug AM Dose PM Dose

200mg 200mg Hydroxvchloroquine (or Placebo)

13000m1-g Vitamin C

30001U Vitamin D

Zinc 0mg

Table 22

[001441 Day 7: The patient is called and asked whether there have been any adverse

events and/or serious adverse events, the list of prior and concomitant medications is updated,

the patient is asked about symptom resolution or progression, and the patient then collects a

nasal swab. The patient also completes their AM and PM diary entries and collects their vital

signs. The patient takes the prescribed regiren outlined in Table 23.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 200mg 200mg 22

:3000m, Vitamin C

3000IU Vitamin D

Zinc 0mg

Table 23

[001451 Day 8: The patient completes theirAM and PM diary entries, collects their vital

signs, and takes the prescribed regimen outlined in Table 24.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 1 200mg 200mg

3000mg Vitamin C

30001U V Itammi D

Zinc Dmg

Table 24

[00146] Day 9: The patient completes their AM and PM diary entries, collects their vital

signs, and takes the prescribed regimen outlined inTable 25.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) 200mg 200mg

Vitamin C 3000mg

Vitamin D 0001U

Zinc 50mg

Table 25

[001471 Day 10: The patient is called reminded to decrease dosage of vitamins C, vitamin

D, and zinc tomorrow. The patient is asked whether there have been any adverse events

and/or serious adverse events, the list of prior and concomitant medications is updated., and

the patient is asked about symptom resolution or progression. The patient also completes their

AM and PM diary entries and collects their vital signs. The patient takes the prescribed

regimen outlined inTable 26.

Drug AM Dose PM Dose

Hydroxychloroquine (or Placebo) |200mg 200mg

Vitamin C I3000m

Vitamin D 3000iU

Zinc 50mg

Table 26

100148] Day 11 to Day 13: The patient completes their AM and PM diary entries and

takes the prescribed regimen outlined in Table 27.

Drug AM Dose PM Dose

Vitamin C 1500mg

Vitamin D 15001U

Zinc 25mg

Table 27

[00149] Day 14: The patient is called and asked whether there have been any adverse

events and/or serious adverse events, the patient is asked about symptom resolution or

progression, and the patient then collects a nasal swab. The patient also completes their AM

and PM diary entries and collects their vital signs. The patient takes the prescribed regimen

outlined in Table 28.

Drug AM Dose PM Dose

Vitamin C 1500mg

Vitamin D 1500IU

Zinc 25rg

Table 28

100150] Day 15 to Day 30: The patient completes their AN and PM diary entries and

takes the prescribed regimen outlined in Table 29.

Drug AM Dose PM Dose

Vitamin C 1500mg

Vitamin D 1500U

Zinc 25mg

Table 29

100151] Follow-Up Period: Month I (outpatient only AFTER negative test): Vital signs

are taken (BP, -IR, RR, oxygen saturation. temperature), the patient is assessed for adverse

events and/or serious adverse events, and EKG is administered as well as physical exam and

a blood draw for CBC/Complete metabolic panel/C-Reactive Protein. The list of prior and

concomitant medications is updated and anasal swab is collected.

[001521 Month 2 (outpatient): Vital signs are collected (BP, HR, RR, oxygen saturation,

temperature) the patient is assessed for adverse events and/or serious adverse events, and

EKG is administered as well as physical exam and a blood draw for CBC/Complete

metabolic panel/C-Reactive Protein. The list of prior and concomitant medications is

updated.

[00153] Month 3 (outpatient): Vital signs are taken (BP, HR, RR,oxygen saturation,

temperature), the patient is assessed for adverse events and/or serious adverse events, and

EKG is administered as well as physical exam and a blood draw for CBC/Complete metabolic panel/C-Reactive Protein. The list of prior and concomitant medications is updated and a nasal swab is collected.

[001541 COVID-19 Sample Collection Procedure is the same as that outlined above in

prior Examples. Table 30 outlines the schedule of events for Example 4.

Assessment Informed Consent & X Demographics Make list of x x X X X prior and Xx x concomitant medications Confirmation of Positive PCR for COVID-19 Review of Medical X Records Prescription of Antimicrobials x

Provide home health X equipment Pregnancy test' X Call Subject at X X X home Vitals at home x x X x|X X X X X Subject will X x x x x x x x complete X x x x x AM/PM diary Hydroxychloro X X X X quire 200mg BID (or placebo Azithromycin X 500mg (2 tablets) once daily (or placebo) Azithromycin 250mg(1 X N X x tablet) once daily (or placebo) Vitamiin C X XX 3000mg (4 X X: X X X X capsules) once daily Vitamin ) X XX 30001U (4 X X: x x X X capsules) once daily Zinc 50mg (4 X X capsules) once X X X X X X X Claily Vitamin C X X X X X 1500mg(2 capsules) once daily Vitamin D X X X X X 1500IW(2 capsules) once daily Zinc 25mg (2 XX x X X capsules) once daily Ask about AE X X X X X and SAE Vitals in- X X X clinic Physical exam XX X EKG in-clinic X XX Swabs for RT- N X X X PCR Bloodwork' X XX Reviewlistof X X X X X XX X X X x X X X x prior and concomitant ineations Table 30

[001551 Regardino Table 30: The antimicrobials include hydroxychloroquine 200mg

tablets (#20), azithromycin 250mg tablets (#6), vitamin C 750mg capsules (#80), vitamin D

7501U capsules (#80), zinc 12.5mg capsules (#80); the home health equipment includes an

EKG (worn continuously), pulse oximeter, and thermometer the pregnancy test is

administered if thepatient is a woman of childbearing potential; the patients are called at

home to remind them to collect swabs for RT-PCT, ask about AE/SAE ask about symptoms,

and answer any questions; the vitals taken at home include an EKG, oxygen saturation, and

temperature; the vitals in-clinic include height (only at first visit), weight, blood pressure

(following5minutessitting)pulse,respiratory rate temperature, and oxygen saturation; and

the bloodwork includes CBC, Complete Metabolic Panel, and CRP (details in section 9

Sample Collection).

100156] Statistical Analysis: The treated patients in this study are compared to the placebo

group. Measurements include PCR test results, presence or absence of symptoms, and

symptom severity. PCR results will be compared between the groups as positive or negative

[001571 In this study, the meaningful threshold is calculated as mean change in clinical

symptoms as recorded in the diary, from Day I through week 12. Each category in the diary

is assigned a number, 0 for None, I for Mild, 2 for Moderate and 3 for severe. Each category

is analyzed independently and as a group. Ultimately, efficacy is determined based upon

reduction and/or progression of symptomatic days, reduction of symptom severity, as well as

analysis of the subject's RT-PCR testing per protocol. These data are compared to an

existing database of de-identified Subject data.

[00158] The change of these measurements from the end to the baseline (post-pre) are

used as the primary outcome, for example, ie = pei - [eo, where ei and po are the outcome

of Subjects from the treatment group at the end and at baseline, respectively.

[00159] Categorical variables are summarized by presenting the number (n) and percent

(%) of subjects in each category. All Statistical tests for the analysis are performed using the

p<0.05 level of significance. All confidence intervals will be one-sided

[001601 Sample size was calculated as follows:

n= log B

log p

[001611 Where l = the probability of a Type II error

[001621 p = the proportionof the populationNOTaffected

[001631 The proportion of the population affected by COVID-19 is 0.005 percent, thus

0.995 percent aren't affected

[001641 The probability of a type II error is 0.05

100165] Thus:

[001661 n=::: lou 0.050

100167] log 0.995

[001681 n:=597.647

[001691 A sample size of 600 was used.

[001701 Example 5: Successful Treatment of COVID-19 Infected Outpatients and

Prophyla xis ofImmediate Associates

[001711 Objective: to successfully treat COVID-19 infected outpatients and prophylaxis

of immediate associates.

[00172] Procedure: Prospective COVID-19 infected individuals were diagnosed using a

Pangea DNA/RNA Shield" Collection Tube to obtain a nasopharyngeal swab and PCR +ve

patients were entered into the study. They were immediately commenced on a 10 day course

of Hydroxychloroquine (200 mg, twice a day, for 10 days), Azithronycin extended release

(500mg on day 1. then 250 mg a day for days 9-10). zin (50mgadayfordays1-10),

Vitamin D (30001U a day for days 1-10) and Vitamin C (3000mg a day for days 1-10). Some

individuals lived alone; otherwise immediate partners and family deemed to be most exposed

were given a prophylactic which comprised hydroxychloroquine200 mg twice a day on day I

only with Zinc. Vitamin C and Vitamin D for given at the same doses as above for days 1-10.

[001731 Results: In 11 families a total of 21 family members were identified to be PCR

COVID-19 positive index cases and were treated with the above treatment protocol while 22

exposed associates with negative PCR were given the above prophylaxis protocol. This is

shown below in Table 31. All 21 index cases were cured of COVID-19 infection asjudged by the repeat swab PCR on day 10 and accompanying symptom resolution. None of the 22 highly exposed associates developed COVID-19 infection when retested on day 10 (day 14 in

Family 10) in spite of close co-habitation with the infected index cases. Table 31 documents

the results from families that received a 10-day course of daily HCQ (200mg bd), AZ

extended release (500mg dayl, then 250 mg zinc(50mg), Vitamin D (30001U) and Vitamin

C (3000mg)

Family Patient/s Age (years)- Comorbidities of the After treating with After treating treated sex of the patients HAZDPAC Cured/ ZINCD±H family patient PCR test member positive/negative/ prophylaxed other synptons

#1 1 23 male Asthma Negative PCR - day Parents overweight, 10 diabetes, father with heart disease never got the disease

#2 3 60- male All 3 patients cured Mother didn't get (father) the virus

18- male (sonl) Asthma

16- female (daughter)

#3 1 40-female Avoidedintubation Sever multiple Husband did not by leaving hospital symptoms resolved turn positive at home

#4 2 78- male BCG-COPD, Both cured Daughter, son-in diabetes, heart law and 2 grandkids disease (heart didn't catch the surgery month prior virus

77-female Pacemaker, BCG

"5 3 56-male Unable to eat or Started treatment on Wife never got the drink day 10. Sever disease symptoms resolved

Cured 27- male

24- female Asthma

6 1 56- female Admitted to hospital Husband never got sent home, as two thedisease kids weresick with fever. Ml recovered with vitamins

#7 1 44-female Cured, autoimmune Husband and 4 kids issues started never got the disease

#8 3 52- female Lupus Cured Bofriend(54y) with Diabetes, son 53-male Cured 18) and daughter

19- male Severe asthma Cured 1(16) never got the disease

92 45-female Both cured from Husband and severe symptoms of daughter never got 16-male cough and fever the disease

#10 2 44- male Cured from loss of Mother (50y) never smell, fever, cough got the disease

Cured 25- female Partially treated with 21-female HAZDPAC - slowly turned - ve

#11 I 33-female No ICU nurse recovered Boyfriend never got the disease

Table 31

100174] Apart from the families a further I Isingle infected individuals found to be swab

PCR positive were treated with the above treatment protocol. This is shown below in Table

32. All were also successfully cured of the infection.

Patient Age (years)- sex of the Comorbidities/symptoms of the After treating with patient patients HAZDPAC Cured/not

#1 44-female (no BCG in Asthma Cured childhood)

#2 81- male Diarrhea Cured

#3 52-female Fever Cured

#4 66-male Valve surgery Cured

,5 29-female (no BCG in Ashma Cured childhood)

#6 50-female Auto immune thyroiditis, sever Cured cough and fever

#7 43-male Cough, desaturation of oxygen Curd

#8 53-male Diarrhea, cough, fever, Cured desaturation of oxy gen

#9 44- female Autoimmune history, fever, Cured increase heart rate

:/10 44- female Pneuinothorax discharged from Cured ICU with COVID-19

#11 43- male Fever +ve Covid-19 PCR Cured

Table 32

100175] A further 9 individuals recently closely exposed to Covid-19 infected persons

were given the prophylaxis protocol outlined above. The prophylactic worked very well with

no exposed person acquiring the infection. This is shown in Table 33.

Individual Age (years) & details of the individual After treating with ZINCD+H

#1 Mother of 16 year old child who had Prophylaxed and never got the disease COVID-19

#2 24- female, ICU nurse - multiple Prophylaxed and never got the disease exposures

#3 47- male, cardiologist exposed to +ve Prophylaxed and never got the disease patients

#4 70- male medical director of a hospital Prophylaxed and never got the disease (exposed to numerous doctors with COVID-19)

#5 55- male anaesthesiologist (intubates Prophylaxed and never got the disease COVID-19 patients)

#6 I55- ICU nurse (worked on COVID-19 Prophylaxed and never got the disease floor)

#7 40- ICU nurse many Covid-19 patients Prophylaxedand never got the disease

:""8 53-Doctor with pancreatitis Prophlvaxedand never got the disease

#9 28-Paramedic - healthy Prophylaxed and never got the disease

Table 33

100176] Discussion: It was demonstrated that a 10 day combination of

hydroxychloroquine, azithromycin (for 5 days only), zinc with vitamin D and vitamin C. can

result in uniform cure of COVID-i9 infection when used inan outpatient population. The

prophylaxis treatment noted above for those closely exposed to proven, infected patients can

completely prevent spread of COVID-19. This combination of test-and-treat permits

abolishing of new outbreaks of infection such as a 'next wave' - by avoiding quarantineto

treat the infected and give prophylactics to surrounding staff and family.

[001771 In conclusion, this is an effective anti-Covid--19 therapy as well as an effective

prophylactic combination capable of arresting the spread of coronavirus infection throughout

the comununity, This is achieved by treating the index case and the surrounding associates of

the patient as early as possible after infection is identified arid then treating the people they

live with and close associates.

[00178] Example 6: Presence of the SARS-CoV-2 by NGS of Fecal Samples

[00179] Objective: In view of the large percentage of SARS-CoV-2 detectible by RT

PCR in stools of infected patients, the objective was to identify the presence of the SARS

CoV-2 by NGS of fecal samples from symptomatic study participants positive for SARS

CoV-2 by nasopharyngeal sampleRT-PCR, in addition to asymptomatic individuals (with or

without prior nasopharyngeal sample RI-PCR). The objective was also to execute whole

genome analysis to characterize SARS-CoV-2 mutational variations to identify potentially

siRnificant nucleotide changes.

[001801 Procedure: Study participants (n = 14) underwent testing for SARS-CoV-2 from

fecal samples by whole genome enrichment NGS. Following fecal collection (Zymo

Research Shield Fecal Collection Tubes), RNA was extracted (Qiagen Allprep Power Viral

Kit), reverse transcribed (New England Biolabs NEBNext 1st and 2nd Strand Synthesis

Modules), library prepped (Illuinina Nextera Flex for Enrichment), enriched (Ilumina

Respiratory Virus Oligo Panel), and sequenced on Illuinina's NextSeq 550 System.

Sequences were then mapped to the SARS-CoV-2 Wuhan-Hu-1 (NN908473) complete

genome utilizing One Codex's SARS-CoV-2 bioinformatics analysis pipeline. SARS-CoV-2

positive samples were furtheranalyzed for mutational variants that differed from the

reference genome. Of the 14 study participants, 12 also had their nasopharyngeal swabs

tested for SARS-CoV-2 by RT-PCR.

[001811 Results: The results from patients that had their stool samples tested by whole

genome enrichment NGS, and their nasopharyngeal swabs tested by RT-PCR forthe

presence of SARS-CoV-2 were evaluated. Of the 14 study participants, ten were symptomatic

and tested positive for SARS-CoV-2 by RT-PCR, two asymptomatic individuals tested

negative, and two other asymptomatic individuals did not undergo RT-PCR testing (Table

34). Patients 5 and 7, which tested positive by RT-PCR from nasopharyngeal swabs, were

treated with the protocol from Example 5 above (Hydroxychloroquine, Azithromycin,

vitamin C. vitamin D, and zinc for 10 days prior to fecal collection). Similarly, after positive

nasopharyngeal swab, patient 13 was treated with vitamin C, vitamin D, and zinc for 10 days

(the same protocol as noted above in Example 5) before fecal collection. The concordance of

SARS-CoV-2 detection by enrichment NGS from stools among positive non-treated patients

tested by RT-PCR nasopharyngeal analysis was 100% (7/7). Patient 8, who did not undergo

nasopharyngeal analysis, tested positive for SARS-CoV-2 by NGS. The three patients (5, 7,

13) that received treatment prior to providing fecal samples, all tested negative by NGS.

Asymptonatic patients 2 and 9, who tested negative by nasopharyngeal swab, were also

negative by NGS, as was asymptomatic patient 14. Table 34 outlines the symptoms and

SARS-CoV-2 testing results.

Nasopharyngeal J Sample ID Symptoms Swab (RT- Treated Feca] Patin PCR) PCR) (NGS) Location

Patient I febrile, diarrhea, anosmia, 02 sat. <90% + no + PA

Patient 3 febrile. diarrhea, 02 sat. <90% + no + CA

Patient 4 febrile diarrhea, anosnia, 02 sat. <90% + Io + AZ

Patient 6 febrile cough, anosmia + no + AZ

Patient 8 none n/a no + CA

Patient 10 febrile, cough, headache + no + GA

Patient It febrile, cough, headache + Io + GA

Patient 12 febrile, cough + no + GA

Patient 5 febrile, cough + yes - CA

Patient 7 febrile, cough + yes - GA

Patient13 febrile, cough + yes - GA

Patients none - no - CA

Patient 9 none - no CA

Patient 14 none na no - CA

Table 34

[001821 All fecal samples analyzed by enrichment NGS from positive patients by RT

PCR, achieved 100% genome coverage of SARS-CoV-2 except for patient 3 which had 45%,

and patient 10 which had 93% coverage. Table 35 outlines the enrichment NGS metrics.

\inph ID Genome # Variants Mapped MeanDepth Coverage (over 1Ox) Reads

Patient100% 1 465645 1129.8x

Patient 3 45% I1 5984 31.7x

Patient 4 100% 9 131582 318.6x

Patient 6 100% 10 793603 1924.6x

Patient 8 100% 10 496852 1206.7

Patient 10 93% 9 5929 15.6x

Patient11 00% 10 1270734 3075.3x

Patient 12 100% 10 38256 92.7x

Table 35

100183] The total number of SARS-CoV-2 mapped reads for patients 1, 3, 4, 6, 8, 10,

1l, and 12 were 465645, 5984, 131582, 793603, 496851 5929, 1270734. and 38256

respectively.The mean read depths of SARS-CoV-2 for patients 1, 3, 4, 6, 8, 10, 11, and 12

were 1129,8x, 31.7x, 318.6x, 1924.6x, 1206.7x, 15.5x, 30753x, and 92.7x, and respectively.

The read depths at specific coordinates along the SARS-CoV-2 genome for each patient are

captured in Figures 5A-5H. Whole genome alignment of SARS-CoV-2 inpatients 1, 3, 4, 6,

8, 10, 11, and 12 (respectively) as identified by One Codex's SARS-CoV-2 analysis pipeline.

The x-axis depicts the genomic coordinates as aligned to the MN908947.3 reference genome,

and the y-axis represents the read depth at specific loci.

[001841 Following alignment and mapping of SARS-CoV-2, patient genomes were

compared to theWuhan-Hu- (MN90847.3) SARS-CoV-2 reference genome via One

Codex's bioinformatics pipeline to identify mutational variations. This analysis identified

nucleotide variants at positions nt241 (C- T) and nt23403 (A-> G) across all positive

patients, and variants at positions nt3037 (C - T) and nt25563 (G-> T) in seven of the eight

patients (Table 3). Interestingly, patients 8, 11. and 12 harbored the same set of variants, as

did patients 4 and 6 (who were kindred). Unique variants not identified in any of the other

individuals were detected in patients 1, 3, 6, and 10, withpatient 3 harboring the most distinct

SARS-CoV-2 genome with eight unique variants, followed by patient I with seven.

Collectively, there were thirty-three different mutations among the patients in which SARS

CoV-2 was detected by whole genome enrichment NGS. Table 36 outlines the SARS-CoV-2

genornic positions, variant changes, and frequencies across the positive patient cohort.

o V t Patient Patient Patient Patient Patient Patient Patient Patient Region ORF P 1 3 4 6 8 10) 11 12

5 U'TR 241 C-+ T 100% | 100% 100% 100% 100% 100% 100%/s 100%

la 833 T- C x x x x 100% x 100% 100%

a1059 C- T x 100% 100% 99% 100% i0% 100%

a158 C-+ T x 100% 100% x x N

a 1973 C -T x x 87% x N N

a 3037 C - T 100% x 100% 100% 100% 1009% 100% 100%

'a3028 C i x 89 x x x x N

la4866 G-±I 725W x N N N N

'a 6720 C- T 93% x x x x x x x

la 8102 G - x I00% x x x x x x

la 9401 -> c x x x x x 64% x x

la 9403 T --- A x x x x x 64% x x

la 10870 G - T N 100% 100% x x x x

la 11123 G --+A N 100% 100% x x x x

lb 14408 C- T 100w x 100% 100% 100% x 100% 100%

lb 14822 C-> T x 100% x x x x x

lb 16616 C --- + T N x 100% x 100% 100%

lb 16848 C -T 100% x x x x xx x

lb 18652 C -A N N N x 83% x x

lb 19989 TI-+EG N |00% x N N N x N

Spike 21576 T - G x 83% X N x x

Spike 23264 G -+A X 75/ X N N x x

Spike 23403 A -+G 100% 100% 100% 100% 100% 100% 00% 100%

Spike 23603 x x x x x

3a 25563 G -r x 100% 100% 100% 100% 100% 0 100%

3a 25976 C->A x x x x 100% x 100% 100%

8 27964 C-+ x x x 100% x 10% 100%

Nucleoprotein 28881 G -A 1001 x x x x x

Nucleoprotein 28882 G -A 1001 x x x x x

Nucleoprotein 28883 G -+ C 100x x x x x x

Nucleoprotein 28997 C - T x 100% X x X x

Nucleoprotein 29019 A- T x 100% x x x x x

Nucleoprotein 29364 C -- G x x x 85% x x

Table 36

1001851 Discussion: Although previous studies have identified SARS-CoV-2 in fecal

collections by RT-PCR, this study was able to report whole genome sequencing (GS) of

SARS-CoV-2 from stool samples. SARS-CoV-2 was identified in patients that tested positive

by nasopharyngeal swab RT-PCR analysis and unique genomes in 62.5% of the NGS positive

patients was observed. The overall homology among the genomes was high (99.97%), with

variations identified in the ORF regions la, lb, S, 3a, 8, and N. Of particular interest, was the

adenine to guanine change in the S protein at position nt23403 which converts aspartic acid

to glycine (D- G).

[001861 Conclusion: Next generation sequencing identified the SARS-CoV-2 whole

genome sequence in 100% of patients with positive nasopharyngeal RT-PCR and did not

detect it in treated patients, or those with negative rt-PCR. These results highlight the

importance of metagenomic analysis of the SARS-CoV-2 viral genome.

[00187] Example 7: Randomized, Double-Blind, Placebo-Controlled Phase IIA Study of

Hydroxychloroquine, Vitamin C, Vitain D, and Zinc for the Prevention of COVID-19

Infection

[00188] Qbjecives; Prevention of COVID-19, Lack of COVID-19 symptoms, and

assessment of safety and tolerability

[001891 Procedure: Screening Period (Days -7 to -1): Prescription of home health

diary. There are two groups being studied: Arm I and Arm 2.

100190] Arm I is prescribed the following antimicrobials: hydroxychloroquine 200mg

twice a day for I day only, vitamin C 300011 per day for 12 weeks, vitamin D 30001per

day for 12 weeks, and zinc 50mg per day for 12 weeks. The zinc can be reduced to 25 mg if

GI upset occurs. The hydroxychloroquine is to be taken first thing in the morning as soon as

subject has eaten and again right before bed, and must be separated from vitamin dose by at

least 2 hours.

[001911 Arm 2 is prescribed the following antimicrobials: Placebo twice a day for I day

only, vitm C 30001U per day for 12 weeks, vitamin D 30001U per day for 12 weeks, and

zinc 50mg per day for 12 weeks. The zinc can be reduced to 25 Ing if GI upset occurs.

[00192] Day 1: Patient is called to teach them how to use the diary in the EDC, discuss

the medication regimen, and answer any questions they may have. Patient takes pregnancy

prescribed treatment regimen Table 37 outlines the prescribed treatment regimen for Day 1.

Drug AM Dose PM Dose

Hydroxychloroquine (or placebo) 200mg 200mg

Vitmi C1500mg 1500mg

5001UT 5001UT Vitamin D

25mg 25mg

Table 37

100193] Day 2: Patient collects a temperature reading, completes their diary, and is called

on the phone for assessment of any adverse events or serious adverse events, assessment of any COVID-19 symptoms, the list of prior and concomitant medications is updated, any questions the patient has are answered, and the patient takes their prescribed treatment regimen. Table 38 outlines the prescribed treatment regimen for Day 2.

Drug AM Dose PM Dose

Vitamin C 1500mg 1500mg

VitaminD 15001U 15001UT

Zinc 25mg 25mg

Table 38

[001941 Days 3-10: Patient collects a temperature reading, completes their diary, and

takes their prescribed treatment regimen. Table 39 outlines the prescribed treatment regimen

for Days 3-10.

Drug AM Dose PM Dose

Vitamin C 1500mg 1500mg

Vitamin D 1500iU 15001U

Zinc 25mg 25mg

Table 39

[001951 Day 14: The patient is called for instruction on how to collect a nasal swab and

concomitant medications, and answering any questions the) may have.

[00196] Week 3: The patient is called for assessment of any adverse events or serious

adverse events, assessment of any COVID-19 symptoms. updating their list of prior and

concomitant medications, and answering any questions they may have. The patient takes a

temperature reading, completes their diary, and takes the prescribed treatment regimen.

[001971 Table 40 outlines the treatment regime for week 3.

Drug AM Dose PM Dose

Vitamin C 1500mg 1500mg

VitaminD 15001U 15001U

Zinc 25mg 25mg

Table 40

[001981 Week 4: The patient is called for assessment of any adverse events or serious

adverse events, assessment of any COVID-19 symptoms, updating their list of prior and

temperature reading completes their diary. and takes the prescribed treatment regimen. The

patient also collects a nasal swab.

100199] Table 41 outlines the treatment regime for week 4.

Drug AM Dose PM Dose

Vitamin C 1500mg 1500mg

Vitamin D 1500IU 1500IU

Zinc 25mg 25mg

Table 41

[002001 Weeks 5-11: The patient is called weekly for assessment of any adverse events or

a weekly temperature reading, completes their diary, and takes the prescribed treatment

regimen.

[00201] Table,42 outlines the treatment regime for weeks 5-11

Drug AM Dose PM Dose

Vitamin C 1500mg 1500mg

VitaminD 15001U 15001U

zinc 25mg 25mg

Table 42

100202] Week 12: The patient presents to the clinic (or video conference) for evaluation

that includes assessment for adverse events and serious adverse events, updating their list of

prior and concomitant medications, a physical exam, nasal swab collection and COVID-19

sample collection.

100203] Samples for COVD-19 testing are collected using synthetic swabs with plastic

shafts. Nasal swabs ire collected and immediately placed into a sterile vial with 2-3 mL of

and picked up for shipment to the central laboratory. Samples are tested by RT-PCR

[002041 Table 43 presents the schedule of events for Example 7

01

00

Assessment Informed Consent & Demographics X Initial Review of Prior and Concomitant Medications X Medical Records review, including baseline EKG X Randomization X Prescription of Hydroxychloroquine or placebo, vitamin C, vitamin D, andzinc Provision of daily diary, thermometer and pregnancy test Pregnancy Test if applicable X Temperature at home X X X X X X Y X X X X X X X Complete daily diary X XI X X X X IX X X X X X X X

Hydroxychloroquine 200mg X Vitamin C 3000mg X X X X X X X X X X X X X X Vitamin D 3000 1U X X X X X X X X X X X X X X Zinc 50mg, X x X X X X x X X X X X X X Phone/video call to patients x X x X X X x X X x X X X Update list of prior and concomitantmedications X X X X X X X X X X X X x X Ask about AE and SAE X XX X XX X X X X XX X X Assessment of COVID-19 symptoms X X X X X X X X x x X X X X Swabs for RT-PCR X X X X Vitalsin-cflinic X Physical Exam X

Table 43

[002051 Regarding Table 43: The Zinc may be reduced to 25mg if C upset occurs,

height, weight, blood pressure (following 5 minutes sitting) pulse, respiratory rate,

temperature, and oxygen saturation.

[002061 StatisticalAnalysis: The treated patients in this study are compared to the

and symptom severity.

100207] The change of these measurements from the end to the baseline (post-pre) are

used as the primary outcome, for example, pe = pel -pe0, where pel and e0 are the

100208] IOh A< &, aUiSt H , A>£`0 where 0 is a clinicallymeaningful

threshold to measure the disease symptoms. In this study, that meaningful threshold is

through week 12. Each category in the diary is assigned a number, 0 for None, I for Mild. 2

[002091 Categorical variables are summarized by presenting the number (n) and percent

p<0.05 level of significance. All confidence intervals are one-sided.

[002101 Since these are healthcare workers who are exposed to COVID-19 at every shift,

recorded in the patient diary via EDC.

100211] Exanple 8: Method of Treating COVID-19 Infection -with Ivermectin

(ZIVERDOX)

100212] A total of 6 patients infected with COVID-19 were treated as follows:

[002131 Day 1: 12-18 mg/day Ivermectin, 200 mg. Doxycycline twice a day, 250

10,000mg/dayVitarinC, 1,000-100,000 IU/dy' Vitamin D,and 5mg-100mg/diyZinc

[002141 Days 2 and 3:200mg Doxycycline twice a day, 250-10,000mg/day Vitamin C,

1,000-100,000 IlU/day Vitamin D, and 5mg-I00mg/day Zinc

[002151 Day 4: 12-18 mg/day Ivernectin, Doxycycline, Vitamin C, Vitamin D, ad Zinc

[002161 Days 5, 6 and 7: 200mg Doxycycline twice a day, 250-10,000mg/day Vitamin

C, 1,000-100,000 IU/dayvVitamin D, and5mg-100mg/day Zinc

[002171 Day 8: 12-18 mg/day Ivermectin, Doxycycline, Vitamin C, Vitamin D, and Zinc

[00218] Days 9 and 10: 200 mg Doxycycline twice a day, 250-10,000mg/ day Vitamin C.

1,000-100,000 U/day Vitamin D, and 5mg-I00mg/day Zinc

[00219] All 6 patients tested positive for COVID-19 antibodies at day 5

[00220] All 6 patients tested negative PCR at days 5-7.

[00221] Basic information about the 6 patients is shown in'Table 44.

............ a. l. 4 4.... . . . . .

........... * .. . ............ ~i~$~Co . . . . . . . . . . .

.......... , .............. .................. ......................................................

Table 44

[002221 Example 9: Study evaluating method of prevention (ZINCD+H)

100223] As of January 14, 2021, a total of 91 individuals have been treated with the

method of prevention of the claimed invention. These 91 individuals were high risk either

from potential exposure at work or from living with people who had tested positive for

COVID-19. Of those 91 individuals, 59 individuals gave consent for the test information to

be released. Of those 59 individuals, 56 individuals had negative test results, two individuals

had positive test results but were asymptomatic, and one individual had an invalid test result

after receiving the prevention protocol.

[002241 In view of the above, it can be said that 58 out ofthe 59 individuals were

successfully treated with the prevention protocol. That is a success rate of about 98%.

[002251 Table 45 details the information presented above. In Table 45, the results are

color coded as follows:

c. There was only one invalid test result for PRG42-070 on 11/14/2020 d. PCR tests that were not submitted are not coded.

ARM 1002 J 0 PRG42-004 2 ARM R k C____ T PRG42-003 PRG42-00_2032 3//2020 7/3/2020 7/29/2020 742 9/27/2020 2002

_________ 10,032 1003 ARM ARM I JM TD PRG42-004 PRG42-007 00 7/3/2020 7/16/2020 78/5/2020 9/30/2020 2003

M M PRG42-006 . 7/3/2020 7/16/2020 8/5/2020 9/30/2020 1004

MARPG4- 2004.3 M77 22 7/16/2020 8/1/2 020 1/3/2020 ARM J M PRG42-008 7 16/2020 7 / 0 1/13/202 SCREEN B 0 PRG42-009 FAILURE

________I SAC RE E MPRG42-013 W

A PRG42-015 01/0 C

C SK PRG42-016

E F PRG42-013 W

ARM $1/OO9i~2 C W PRG42-019 W/;/D2 0 K PR(~2002

A- K---- PR342 0)15 ____

MO LP PRG42-02216/0K9'/00 1422

ARM K F PRG420174W H A PRG2202

ARM2 22 0 R PRG42-01881i308/52~ /W7 1922 ____ _________ 210

S RG)~ARM 1":/10/202 A F PRG42-029 ___ __ ______ 10017 ARMI E K PRG42-020 /1/2020 ~ S/All' 9//202 11/122 200720 A 0 PRG42-0321

MDLPRG42 A11/4/0 L B PR4--2 /SA2 *9/0/02 D~ I/Il0)

NO F F PRG42-034 CONSENT

M K PRG42-035

S 0 PRG42-039 ulct

m S PRG42-037 //00 //0O 9/922

' ARM 2 M K PRG42-04231//00 1/202 1722 1682 12/12/23 P CD PRG42-039 AR :l::19 9/0/02 9b02 1013

A PRG42-045

D S PRG42-047 0- 0

ARM12120 S H PRG42-0428i1'/-)1

ARM 12/25/202 SF R PRG42-0531 //20 110/2020 11/1202

P. L PRG42*-05340*121/0O /122

A P PRG42-0'4

A P PRG420556N ___ ___ ________CONSENT ______ _____

0 S PRG42-047_____W 102 0R40*N

-- - - - ---- -------------------------- -------------------- ----------------------- ---------------------

H K PRG42-048 ARM V 10221/52217//U0 12P2

ARM J C PRG42-060 WD 1024 NO R CJ PRG42-061 CONSENT ARM P S PRG42-062 11/ 5/020 11//2020 1214/2L0 1/27/2021 2020 ARM S M PRG42-063 11/2020 11/18/2020 1214/2020 1/27/2021 1020 ARM M C PRG42-064 1020 11/18/2020 12/4/2020 1/27/2021 1023 No H M PRG42-065 CONSENT

CJ B PRG42-066 101//2020 1217/2020 10 2/1/2021 1025 R M PRG42-067 CU 6 1WD 1/222 ARM S V PRG42-068 12//2020 117/2020 12 202 2/4/2021 2019 ARM c F PRG42-069 1 /2020 1/26/2020 1212 22 2/41/2021 1026

C B PRG42-070 11/14/2020 11/27/202 1 3 2/5/2021 2021 ____ _ 10100 ARM A__ I___ S K PRG42-071 ARM 1/21/2020 12/4/120-0 12/20/202 3/1/2021 1027 ARM M C PRG42-072 1/22 12/3/20 12/1192020 2/11/2021 2022 ARM R B PRG42-073 122/12/2021 1029 ARM J G PRG42-074 12/22 12I/22 :2/2/202 2/19/2021 2023 ------- ------ ------ ------ - ----- ------ ------ ------ ---- - ------ ------ ------ -----

ARM L C PRG42-075 124/ 0 1/202 1 1522 1030 11222 ARM T H PRG42-076 24220 12 /12201221 1222 2/501 /S22 1031 ARM V A PRG42-077 124200 1/72020 1/2/2021 2/25/2021 2024 ARM J H PRG42--078 28220 2/122 1622 3/1/2021 2025/621 ARM K H PRG42-079 12822 22 001/6/2021 3/1/2021 1032 M IC PRG42-080 IWD C A PRG42-081 CU 3 202,U0_ 1/6/2021 3/1/2021 ARM P H PRG42-082 22 12/2-5/2020 1/10/2021. 3/5/2021 1033 ARM I M C PRG42-083 2 22 12/28/2020 1/1.3/12021 3/8/2021. 2027

D L PRG42-085 WD

ARM G R PRG42-086 A 202 1/1/2021 1/17/2021 3/12/2021 1035

E G PRG42-087 A2RV 1202 1/1/2021 1/17/2021 3/12/2021 2028 S M PRG42-088 WD *AR1 ARM S E PRG42-089 1/7/2021 1/23/2021 3/18/2021 1036 ARM E G PRG42-090 2 -/2 2 1/5/2021 1/21/2021 3/16/12021 2029

J V =PRG42-091 :2 2 '* 1/7/2021 1/23/2021 3/118/2021 2030

Table 45

[002261 As shown above the prevention protocol of the claimed invention is extremely

effective.

[002271 Example 10:StudyEvaluatingMethods ofTreatmentand Prevention

100228] In a second selection of studies, 25 different households/infection events were

monitored/treated, where at least one person tested positive for COVID-19, and at least one

housemate/familv member!ttendee was treated with a prevention protocol of the claimed

invention. Specifically, there were 155 individuals total in the 25 households/events, with 75

of those 155 individuals testing positive for COVID-19, andthe remaining 8 individuals

were given at least one of the prevention protocols of the claimed invention.

[002291 The treatment protocol was HAZDPAC = Hydroxychloroquine, azithroiycin,

vitamin C, vitamin D and zinc administered as noted above in Example 3.

[002301 The prevention protocols included:

[002311 ZIVERDOX = Ivermectin, doxycyclin, vitamin C, vitamin D, and zinc

administered as discussed above in Example 8.

[00232] ZINCD = zinc, vitamin C, and vitamin D administered as noted above

[00233] ZINCD+H = zinc, vitamin C. vitamin D, and hydroxychloroquine

administered as noted above.

[002341 Table 46 documents all of the data summarized above.

CON71D Tx or HAZ Zn'ER ZINC ZINC PCR ab Group Sex +/- Prophy Dpac DOX D 1) +H repeal 3 Presence months 'V i3-1 4- Tx X negative positive

Neg Prophy X negalive negative I moul

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Female I Tx X negative positive

Male Prophy Neg X negalive negative 7 Kid I PTOPIIN Neg X negative Regative Kid 2 Prophy Neg X negalive negative Kid 3 Prophy X . . . . . . . . . . . . . . . . . - negative Neff negative Kid 4 Prophy Neg X negative ne- ive Male Tx X I negative positive ?F? TX X - m- -- negative _ .-::::::::: Posiuve Male Tx X negati%,c positive 8 Male I None negative Posiuve Male Neg Prophy X negati%,c Ilegatn'e Male A, ,[ ,X ................................................................................................................................................................................................................................ X negative positive ................................................................................................................................................................................................................................ ..*..*. *. *. *. *. *.*,**..*. *. *. *. *. *. *. *.*.*.*.*.*.*.*.*. ........... ::::::: .*******************************. *.*,..... *.*:*:*:*:*:*:*:*:*:*:*:*:*:*:*:*:***********************************************************************..*. *. *. *. *. *. .. .

P ... w x xV * Oog w

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negative positive

Son negati%,c positive 12 Sib I Ne- prophy negative neoative Sib 2 Neg Prophy negati%,c negatn'c Ilisband Ne- ................. PrOPI)y negative ncoative ....7 ........................................................................................................................ ............... .............. .............................................................. ....................................... ....... ................................................................................................................... ......... ........................................................................................................................................................ ................... 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................................................................................................................................................................................................ ......................................................................................................................................................................................................................................................................................................................... ..................... .. . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. :::: ........ .. . . .. . k .................................- .............................................................................................. ........................................................................................................................................................................................................................................................................................................... ........ ------. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .............................................................................. ........................................................................................................................................................................................ ............................................................................................ ............................... x x x x x x x x x x - .................. * * * * *. * . * . * . * . * *. * . * . * : * ******- * - * - * - * - ..... ................................... .................... . . . . . . . . . . . . . . . . . . . ................................ ..................... ::: " -*-.:*-*.. .h w t. . .. : . , :...................... * . * ....... . * . * . * . * . * . * . * . ......* . * . * . * . * . .............. ................................................................................................................................................................... ...................................................................................................................................................................................................................................................................................................................................................... . . . . ..--.-. . . - ............................................................................................................................................................................................. *****.. . . ............................. ........:::::::: ** .......::..................... x .. . . . . . . iiiiiiiiiiiiiiiiiiiiiiii:.:: . . . . . . . . ..................... .................... ....... ....... ......................... .................................. ............... ............. .. .. .. . . . . . . . . . .. ........ .................................... . ...... . ::::::........ . ........................... **-$ ` ..... ') ***R",..2 . . , ********** .......... 6..*. ........... ................ . . . . . . . .............. . .:::::::,. . . . . ......... . . . ..:::::::::: :****X .:.:.:.:.:-:-:-:-:-:-:-:-:-:-:-X .:.:......... : .... . -.: ............................................................................................................................ :....... . . . . ............................................ :.:.:.:.:.:.:.:.:.:.:.:. ..................................................... . .'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'......... ............................................................................................................................................................................................................................................................. '.'. ..,. .... .. .. .. .. .... . . ........................ . .:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:.:. y.,....:..!.:....".. .:...:...:...:.:.:...... . . . . . . . . . ..................................................................... .:.:.::.:.:.:..::..:.::..::.:..::.:..::..:.:lu :..::.:...::..:.::..:.:.,*:..:.i..:i..i.:i.:a.leW.w-.*X.."..-- .jij.i i m ... . . o.ij.iji.jij.iji... ....... ::I ....... .............................................................................................................................. o r , 0 ..... ............................................................................................. . ' * : ....... .......................................................................................................................................................................... ....... ............................................................................................... ....... .......

. male A, ,[ ,x ........................... negative Positive 20 Dentist ..... . . . . . . . . . . . . . . . . . . . -. . . . . . . . . . . . . . . . . . . . . . .- . . . . . xx........ ................. -x ...............,.,.,.,.,.,.,.,. Moir! ......................,.,.,.,.,.,.,.,.::::::: Neg ...................... ................................................................................................................................................................................................................................................................................................................................... Prophy ,.,.,.,.,.,.. ,..,. .............................. - -.....- - - -....................... -- ........ ........-..-::::::::::::::::::::::::::::::: - - - -. x . --. . . . ......... ncgati%,c . . . . . . . . .-. . . -. . . .-. . .- -..,........ .... . . . . .-. . .-. . . -. . . .-. . .-, -. -. -,. ...... Ilegative ........................................................ . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . ....... . . . . . . . . . . . . . . ......................................... . . . . . .:::::::*-.**` *-::::::::::::::::r ::::::::::::::x w : ......................................................................................................................................................................... ..................................................... ................................. : .....

, ................................................................................................ . ........ ...... .. . . . . . . . . . . . . . . . . . . . .................................................................................. ................................................................................................. ......................................................- ..- .r X - , ' x x x x :p.........q..t. .. ............... .............. ........... . .::::::::::

. ::j:j:j:j:j:j:j, ............................................................................ I.. . ........ . . . . . . . ....................................................................................................... ....... ...................... ............ ............................ .. ....,. .i....... .. .. .. .....

. :..............,- ................... .................... . : i . l : i : i : i : i : i : j:j:j:j:j:j:j:j:j:j:i : i : i : i : i : i . * . * * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * . * **************. . * . * . * *****. ...-.-.-.-.-................................................................................................................................................................................................................................................................................................. ::: . ...e XXA . . H . . . .: ..:::::::::::::::::::::: ::::::::::::::::::::::: -*- . * . * . ........ * . * . * . * . * . * . * . * . * . * . * . * . . . . . . . . . . ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......... .............................................................. ................................... . . . . . . . . . . . . . . ............ ...................................... ............................................................ ......... ... ................................. .................. ................... .... : : : : .N ,..... :::::::::: ........................- : : : : :: : :........ : :--*p. .r-'-*o-*-* ....... h-**-.................................................................................... . .. .:************" ............................................................ . . . . . . . . . . . . . . . ." ******************************** ..................................................... . .". .". .". . " ........ . . .". .". . " .................................... . . ".'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.'.......... . . . . . . . . . . . . . . ......... ......... . . *..*... ........................ *..*.. .*..*:::::::***** .::............ :.::.::.:.:........... :..*.*****: :::: :::::.............. i. X. .:::::::::::::. :-...................... ix*********************************************t .............. x x x : ***********************************************t x x........................................................................... j. IV........................ .., * . ,.:.::::::::::::::::: *************** .............. . . . . . . . . . . .... .. !......V . * 9 .. .W . ::**** .................. : .... .1 .,. . . . . . . . . . .

. Patient A ::::::::::::::::::::::::::::::;w x l3egative positive 22 Son Neg Daughter NegZ, x negative negative t, Wife Neg x l3egative ..I E3egallve ......................................................................................................................................................................................................................................................................................................................................... ........ ......................................... ..................................... . . . . . . . . . . . . . . . . ..... ............................. " ................... . . :::1 ".:.::::.:. . .-... . . ................................ i .t.:::............. 1..:::::::::::::::::::::::::::::::::::::. ............."..... ..... ... ,:. .*-, .*-.*.-*.-*.-*.*:::::::::: -.*****. . . . ....... . . .......... T ... ..,..",. ................... ..... .,::::::::::::::: . . ..,. .. ... ... .. ... ... ..... ... ... . . . .X.. . . ...... ,:.:::::::::::::: . -.'....................................................................................................................................................................................... .................................................................................. ............. . . . . . . ...................................... ...................................... ..................................................................... ........ .... ............................................................................ ....... ....... ........................ .................................................... ....... ....... X.. . . . . . . . . #.... ::::::::::: .V ,. . .-.. .*:::::::::::::::::: ...... ......................... . . . . . . . . . . . . . P. . ...I...w . . ..,. ....... .* ****** 6 ........V*M:::*..*..*..*. -,***************** ................................................................................................................................................................................................................................ ............................. ..................................................................................................................................................................... ....... ........ . . . . . . ****:::::: .............................................................................................................................................................................................................................................................................................................. x x x x x .T ....... . .... . . ..:::::::::::::::. ....... ................................................................................................................... ........................................................................... .............................................................................................................................................................................................................. *.:.:.:.:.:...:.:.:.:.:.*.*.*.*.*.*.*.*.*.-.[j *............... ............ . . . . :..... ..... x:::.P ..x. ... .... .... : . . . . . . . . ........ ******o * ... ................... ....... ....,,::::::: . . . . . . . . .X...:........................... .................... ... .*::::. *.::::iiiiiiiiiiin ................................... .................................. .....X.... ..... .I* .xl ................. ..... ..i.i.i::.....-..-*.**, . *. ............................................................. -.*.-*: : : : .... .:.:.:.:.: ..,..X.: : : :.:.:.:.:......................................................- :.:.:.:.*.******** :.::::::::::::::. ..*.*................................................. .*.*.*.*......... *........................................................... .*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*....... .*....... .*.............................. .*.*.*.*.*.*.*.*.*.*.*.*.......................................................... :::::::::::::::::::::::-.*j .*: :::::::::::::::::::::::: *.*.*...................................... ....... 4. ..V .*t.*.*iv .*.*.*.**.':iiiiiiiiii .......................................... .......................... . .................................................................................................................... :..*.*:.*.:*.t .:..*:..*:...::...:.:.:..:.:..::..::..::..::..:*- :.*.:.*.*:.. :.-...:.:k-ift

. . ............... ................................................................................................................................. .................... ..................................... . . ... . . . . . . . . . . ............................................ .-. . . :. . .. . ............................................................................................................ . .************::::::*,.*+ ....................................................................................................................................................... *X X X ......... X X T . . . , ................ ....... . . . . . . .................................................................................. . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . ....... . . . . . . .............................................. . . . . . . . ............. .......................................................... .:.*........ .'..'..'..'..'..

. .............. ....... - '

. ........................... ............... ..... . . . . . . . . . . . . . . .. .. ................................................ ................................. .................................. :4::: - ..A- .X. .X. .X. .X. .X. . X. . ..X. .:..... .......................... . * , . * : . * . * . * .................. * . * . * . * . * . * . * . * . * . * . * . * . * . . ". . ... ' ,,:::::::::::::: . . .. . *.. * . * . . * . . * . *. . * . *. *. * .* .* * . . ................................................. . . . . . . .X...................................................................................................... : . . . . . . . . . . * . w . * : .......................... . . :....... ..................................................................................................- iu... . ................. .................................................... ..' ........................................................................................... ..... . . . . . . . . . . . . . . . . .............................................................................................................................................. . ...... ..................................................................... .................................. ........ ....... :.:.:.:.::::::::::::::::::::. :::::::::: ......... I -V .. ..... -O-.:*i*i*i*i:l.% .:.................. - ............ . .w.-.iiiiiiiiiii .......................... ................... .................................. .................................. ..................................... ..................................... ..... .............................................................................................................. x x.P.. ...i*".r.:...*:,*,I-.*.............................. . : . : . : . ........ ::::::::::::::::::.*..*,.*...*:::::::::: : . : . : : . : . : . : . : . : . : . : . : . : . : . : . : . .... .. :.:.:.:.:.:.:.:.:.:.:::::::..T **:::::::............................................................. - .x . . * . - *:::::::::. ..................... : . : . : . : . : . : . . ,% ' : -... ..... ............... ....... ....... ....... ....... ................... ..... .. .. ........................................................................................................................................................................ ....... ....... ....... ....... ....... ................... .. ....... .. .. .. ... . .*....... ............................................................................................. *********. :::::::::::.*.*.*.*.*.*........ 4 ................... . * ....... *.t ......... . ................................. . . . . . :.:.: .. ....... .................. ...... ................ ................................................................................................................................................................................................................................................................................................................................. ...... . . . . . . . ....... . :.::::::::.:.:.:.:.:.: ................................................................... . . . . . . xxxxxxxxxxj ::::::::::::::::::: * [I *.V ..".:.:.:.:.*:.:.... :::: *.:::: .. .... : . : . : . iiiiiiiiiiij : . : . : . : . : . : .10:. : .*: .* . *kft : . : . * . * . * . -A * . * . ***V . * . * . :iiiiiiiiii ' . '*.'.*'.'*.'*. ................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................ : *:*:*:*:*:*:*:*:*:*:*-*-*-*-*-*-*-* ***:........... **.**.**.**.**.**.***. **. **:::::: ::::::::: ........ .................................................................................................. .*..................

* ......................... .................................. ::: .. .*******:.... :::P -- -:::::::::::::::::::i4 . * . * . * . * . * . * * ! .-X.. ' . . i .::::: i . i . i . i . ..... . . . . : .. . . - . - . - . - . - . - . - . - . - . - . - . - . - . - . - ................................................................. - . - . - . - . - . - . - . - . - . - . - . - . - . - . - . - . - ................................................................................................................... . - . - . - . - . - . - . - . - . - . - . - . - - -------................ :.:.:.::::::: :. .. .*.*. . .:.:.:.:.:.:.:.:.:. . . . . ..... .................... ...................................... ....................... ..... .................. . . . . . . . . . . . . . . . ........ . .,\. . . . . . . . . . xxx .. : .................................................................................................................................... . . ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . ........ .................... -'V. . -i. . .:..:j:j:j:j:j:j:j:j:jt) ............... .................. .......................................................................................................................................................................................................................................................................................................................-........... ....................................................................................................................................................................................................................... x x x x x . . . . . . . . . . . . ...... ................... ........ ........ ...... .:..:..:..:..:..:..:..:..*.****. . . .*...;.. .W . . . . .-,-w . . . -- *.. -. . .`:.i i.*i.*.i *i *i . .................................................................................................... .. .......................................................... ..........................................................................................................................................................................................................................................................................................................

. ............. ....... ::Xp .m-*--*-*-*..:..:.*.O-..:.*.*.:..*............... * .......................... ........ . . . . . . . . ....... *::::: . . . . . .................................................................................................................... ....... ... ::::::::::: .......... ..... ...... :. ..... ................... ..................... .. .. .. .. .. .. .. .. .. .. .. .. .. .. . . ...... ............... . . :.... .... :::... .... . . . . ................ . . . ::.::::::---- ::::::* .*.-- ................................................................................................................................................................................................................................................................................... **::::::::::::::::::::::::::: .:............. ....... :.:.:.:.: T . ..x ..:::::::::::::::., x:..................... :.x:.:.:x.*.x.: ............. :x.:.:x.: .:.x:. :X x .r.-... ................................................................................................................ :............................ *............................................................... *.*.*.*.*........ *.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*.*..*..*........ ..*........ ..*..*..*..*..*..*..*..*..*..*..*..*..*..*..*..*..*.-*.-*.-*.-.*-.*-.*..*..*..*..*..*..*..*..*..*........ .*........ .*.*.*............ ...*...*...*...*...... .. .. .. .............. .. -*' .V:.:.I..:.1:...:::i:i:i:i:i:i:i:i:ii .O*k*-*-ft*i.-W.**-*.-V *.*.':iiiiiiiiii . . . . . . . . . . . . . . . ................................. ............. ..................... . . . . ... . . . . ... .. . . . . . .a ..................................................................................................... .****:.***. . . . . . . :. :.*:*:*........ :*:*:....... :*............................................................................................... *. .*.****:. *.:*.:*.:... !*.*.*....... .* ........... ..... .............. ::::::::::::::: ...... . . . . . . . . . ... . .-................................................ ............. -.-.-.-........ -. -. -. -. -. -. -. -. -. -. -. -. -. -. -. -......... . ...................................................................... -.-.-.-.-.-.-.-............................................ -. -. -. -. -. -. -. -. -. -. -. -. -. -. -. -. -. -. -.................. . -. -. -. -. -. -. -. . .. .. . . ........ . . . .. .. .. ..::::::::::: . . . . . . . . . . . . . . . :.-` . . .-`. .-*.**********: ...:.:.:.:.:.*.*.*.**'.********************** ..:..:..:..:..:.*.::.*.::*..::*..::........................ .'*.'.*'.'*.'*.

* * ................... .................................. ::: :::P ... . . . . .................. *:*:*:*:....... ...... *-*-*-*-*-*-*-*****.:... * . .**..**. .*.**..**.. **........... .......... * .......... i .. . .......... :::::. .... .. ............ : .......... ........ .... ....................... . . . ., e.-t.:,*7.:::::::::::::::::::i4 .................................................................................... . . . . . . . . . . . . . . . . ........ ......................................................................................................................................................... .. .................. ........................ ............. ,\ .. , . . . *****. . . . . . . . . ......................................................................................................................... ........ . . . .X .. :. . . . . . . . . . . . . . . . . . . .................................................................................................................... . . . . . . . . . . . ........................................................................ ................................................... ....... ................................................................ ........ . -l0....... ..... ::::: . . . *::::::::::p ........ . . :. : . : . : . : ............ .0 ................8 :1 6 - -V ,.,. . -, , * : .::..*...*..*.. .*. ........... ........................................................ ................. ................................................................................ * ........ ... * * * * ...

. ... .... i P m X* * WI T 6 W . P.M .. . & .. X.... ... 1w W ..... R a 0 W " ... .. W "0 * . . k x 1W P0MUW Xxxxxxx.m ... ...V* ... P m%.. ... xxxx ***PQ **** **RR * t X 1m . . . K . .. ... ... .*Ne e . . .. * A W P K ... xv. wm nT . b . . .. R X Fx. m . N m Q Op " W-- . .. .... ...*... ........ * * ... ... * 4 * T .. " K X a T " pA e ... .. T. .. ". .. PM b N l S * X ... * ... .. ... ...... ...... ....... u . Nm Q Op I .. ... .. .. VO I 0. ... .. T " % W & . P * .l* 7 T. X ... X * ..Vt o A*V**** .. T .. " ... ... X

Patient + Tx X negative negative

MIom Neg Prophy X negative positive 24 Dad Neg Prophy X negative negative Brother Neg Propty X negative negative

Table46

[002351 In all 25 households/events, all 80 individuals who were treated wihthe

prevention protocols tested negative for COVID-19 via PCR at 3 months post exposure and

tested negative for the presence of antibodies. Accordingly, none of the housernates/attendees

in all 25 households/events ever became infected with COVID-19, despite living with at least

one, and some cases multiple, infected individuals.

100236] Having thus described the invention, it should be apparent that numerous

structural modifications and adaptations may be resorted to without departing from the scope

and fair meaning of the instant invention as set forth herein above and described herein below

by the claims.

100237] While particular forms of the invention have been illustrated and described, it

will also be apparent to those skilled in the art that various modifications can be made

without departing from the spirit and scope of the invention.

[002381 Although the present invention has been described in considerable detail with

reference to certain preferred embodiments, other embodiments are possible. The forgoing

description is not intended to be exhaustive or to limit the invention to the precise form

disclosed. Many modifications and variations are possible in light of the above teaching. The

steps disclosed for the present methods, for example, are not intended to be limiting nor are

they intended to indicate that each step is necessarily essential to the method, but instead are exemplary steps only. Therefore, the scope of the appended claims should not be limited to the description of preferred embodiments/methods contained in this disclosure. All references cited herein are incorporated by reference. Insofar as the description above and the accompanying drawings disclose any additional subject matter that is not within the scope of the claims below, the inventions are not dedicated to the public and the right to file one or more applications to claim such additional inventions is reserved.

[00239] It is to be understood that, if any prior art publication is referred to herein, such

reference does not constitute an admission that the publication forms a part of the common general

knowledge in the art, in Australia or any other country.

62 20985047_1 (GHMatters) P119847.AU

Claims

WHAT IS CLAIMED IS: 1. A method of preventing COVID-19 infection in an individual, the method comprising the steps of: a) providing an individual that is not infected with COVID-19; b) administering four antimicrobials to the individual, wherein the antimicrobials comprise: i) administering chloroquine or hydroxychloroquine in a daily dosage range of 20 mg to 2,000 mg; ii) administering vitamin C in a daily dosage range of 250 mg to 10,000 mg; iii) administering vitamin D in a daily dosage range of 1,000 IU to 100,000 IU; and iv) administering zincin a daily dosage range of 5 mg to 100 mg; and c) monitoring the individual's condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19.

2. Use of four antimicrobials in the preparation of a medicament for use in a method of preventing COVID-19 infection in an individual, wherein the antimicrobials comprise: i) chloroquine or hydroxychloroquine; ii) vitamin C; iii) vitamin D; and iv) zinc; and wherein the method comprises: a) providing an individual that is not infected with COVID-19; b) administering the four antimicrobials to the individual, wherein the antimicrobials comprise: i) administering chloroquine or hydroxychloroquine in a daily dosage range of 20 mg to 2,000 mg; ii) administering vitamin C in a daily dosage range of 250 mg to 10,000 mg;

63 20985047_1 (GHMatters) P119847.AU iii) administering vitamin D in a daily dosage range of 1,000 IU to 100,000 IU; and iv) administering zinc in a daily dosage range of 5 mg to 100 mg; and c) monitoring the individual's condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19.

3. The method of claim 1 or the use of claim 2, wherein step b) comprises: bl) administering, on day 1: i) 400 mg of hydroxychloroquine; ii) 3,000 mg of vitamin C; iii) 3,000 IU of vitamin D; and iv) 50 mg of zinc; and b2) administering on day 2: i) 3,000 mg of vitamin C; ii) 3,000 IU of vitamin D; and iii) 50 mg of zinc.

4. The method or use of any one of claims 1 to 3, wherein step b) further comprises before step c), administering ivermectin in a daily dosage range of 12 mg to 18 mg.

5. The method or use of any one of claims 1 to 4, wherein step b) further comprises before step c), administering doxycycline in a daily dosage amount of 400 mg.

6. A method of preventing COVID-19 infection in an individual, the method comprising the steps of: a) providing an individual that is not infected with COVID-19; b) administering four antimicrobials to the individual, wherein the antimicrobials comprise: i) hydroxychloroquine; ii) vitamin C; iii) vitamin D; and

64 20985047_1 (GHMatters) P119847.AU iv) zinc; and c) monitoring the individual's condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19.

7. Use of four antimicrobials in the preparation of a medicament for use in a method of preventing COVID-19, wherein the antimicrobials comprise: i) hydroxychloroquine;

ii) vitamin C; iii) vitamin D; and iv) zinc, wherein the method comprises: a) providing an individual that is not infected with COVID-19; b) administering the four antimicrobials to the individual; and c) monitoring the individual's condition over a pre-determined amount of time to determine the individual does not become infected with COVID-19.

8. The method of claim 6 or the use of claim 7, wherein step b) comprises: i) administering hydroxychloroquine in a daily dosage range of 20 mg to 2,000 mg; ii) administering vitamin C in a daily dosage range of 250 mg to 10,000 mg; iii) administering vitamin D in a daily dosage range of 1,000 IU to 100,000 IU; and iv) administering zinc in a daily dosage range of 5 mg to 100 mg.

9. The method or use of any one of claims 6 to 8, wherein step b) further comprises administering ivermectin in a daily dosage range of 12 mg to 18 mg.

10. The method or use of any one of claims 6 to 9, wherein step b) further comprises administering doxycycline in a daily dosage amount of 400 mg.

11. The method or use of any one of claims 6 to 10, wherein step b) comprises: b1) administering, on day 1: i) 400 mg of hydroxychloroquine;

65 20985047_1 (GHMatters) P119847.AU ii) 3,000 mg of vitamin C; iii) 3,000 IU of vitamin D; and iv) 50 mg of zinc; and b2) administering on day 2: i) 3,000 mg of vitamin C; ii) 3,000 IU of vitamin D; and iii) 50 mg of zinc.

12. A method of treating an individual infected with COVID-19, the method comprising the steps of: a) providing an individual infected with COVID-19; b) administering five antimicrobials to the individual, wherein the antimicrobials comprise: i) administering hydroxychloroquine in a daily dosage range of 200 mg to 1,000 mg; ii) administering azithromycin in a daily dosage range of 250 mg to 500 mg; iii) administering vitamin C in a daily dosage range of 1,000 mg to 10,000 mg; iv) administering vitamin D in a daily dosage range of 3,000 IU to 40,000 IU; and v) administering zincin a daily dosage range of 25 mg to 75 mg; and c) monitoring the individual's condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

13. Use of five antimicrobials in the preparation of a medicament for use in a method of treating an individual infected with COVID-19, wherein the antimicrobials comprise: i) hydroxychloroquine;

ii) azithromycin; iii) vitamin C; iv) vitamin D; and

66 20985047_1 (GHMatters) P119847.AU v) zinc, the method comprising: a) providing an individual infected with COVID-19; b) administering the five antimicrobials to the individual, wherein the antimicrobials comprise: i) administering hydroxychloroquine in a daily dosage range of 200 mg to 1,000 mg; ii) administering azithromycin in a daily dosage range of 250 mg to 500 mg; iii) administering vitamin C in a daily dosage range of 1,000 mg to 10,000 mg; iv) administering vitamin D in a daily dosage range of 3,000 IU to 40,000 IU; and v) administering zinc in a daily dosage range of 25 mg to 75 mg; and c) monitoring the individual's condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

14. The method of claim 12 or the use of claim 13, wherein step b) further comprises vi) administering ivermectin in a daily dosage range of 12 mg to 18 mg.

15. The method or use of any one of claims 12 to 14, wherein step b) further comprises administering doxycycline in a daily dosage amount of 400 mg.

16. The method or use of claims 12 or 13, wherein step b) comprises: b1) administering, on day 1: i) 400 mg of hydroxychloroquine; ii) 500 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; b2) administering daily, on days 2 to 5:

67 20985047_1 (GHMatters) P119847.AU i) 400 mg of hydroxychloroquine; ii) 250 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; and b3) administering daily, on days 6 to 10: i) 400 mg of hydroxychloroquine; ii) 3,000 mg of vitamin C; iii) 3,000 IU of vitamin D; and iv) 50 mg of zinc.

17. The method or use of claim 16, wherein step b3) of administering on days 6 to 10 further comprises administering 250 mg of azithromycin.

18. A method of treating an individual infected with COVID-19, the method comprising the steps of: a) providing an individual infected with COVID-19; b) administering five antimicrobials to the individual, wherein the antimicrobials comprise: i) hydroxychloroquine; ii) azithromycin; iii) vitamin C; iv) vitamin D; and v) zinc; and c) monitoring the individual's condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

19. Use of five antimicrobials in the preparation of a medicament for use in a method of treating an individual infected with COVID-19, wherein the antimicrobials comprise: i) hydroxychloroquine;

ii) azithromycin;

68 20985047_1 (GHMatters) P119847.AU iii) vitamin C; iv) vitamin D; and v) zinc; the method comprising: a) providing an individual infected with COVID-19; b) administering the five antimicrobials to the individual; and c) monitoring the individual's condition over a pre-determined period of time to determine whether the individual is no longer infected with COVID-19.

20. The method of claim 18 or the use of claim 19, wherein step b) further comprises administering ivermectin in a daily dosage range of 12 mg to 18 mg.

21. The method or use of any one of claims 18 to 20, wherein step b) further comprises administering doxycycline in a daily dosage amount of 400 mg.

22. The method or use of any one of claims 18 to 21, wherein step b) comprises: i) administering hydroxychloroquine in a daily dosage range of 200 mg to 1,000 mg; ii) administering azithromycin in a daily dosage range of 250 mg to 500 mg; iii) administering vitamin C in a daily dosage range of 1,000 mg to 10,000 mg; iv) administering vitamin D in a daily dosage range of 3,000 IU to 40,000 IU; and v) administering zinc in a daily dosage range of 25 mg to 75 mg.

23. The method or use of any one of claims 18 to 22, wherein step b) comprises: b1) administering, on day 1: i) 400 mg of hydroxychloroquine; ii) 500 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; b2) administering daily, on days 2 to 5:

69 20985047_1 (GHMatters) P119847.AU i) 400 mg of hydroxychloroquine; ii) 250 mg of azithromycin; iii) 3,000 mg of vitamin C; iv) 3,000 IU of vitamin D; and v) 50 mg of zinc; and b3) administering daily, on days 6 to 10: i) 400 mg of hydroxychloroquine; ii) 3,000 mg of vitamin C; iii) 3,000 IU of vitamin D; and iv) 50 mg of zinc.

24. The method or use of claim 23, wherein step b3) of administering daily, on days 6 to 10, further comprises administering one dose of 250 mg of azithromycin.

70 20985047_1 (GHMatters) P119847.AU

Providing a healthy individual who is

not infected with COVID-19

Administering hydroxychloroquine,

vitamin C, vitamin D and zinc to the

individual

Monitoring the individual's condition

over a pre-determined amount of time

Administering an additional

prescribed dosage of

hydroxychloroquine, vitamin C,

vitamin D and zinc

Fig. 1

Providing a healthy individual who is

not infected with COVID-19

Administering vitamin C, vitamin D

and zinc to the individual

Monitor individuals condition over a

pre-determined amount of time

Administer an additional prescribed

dosage of vitamin C, vitamin D and

zinc

Fig. 2

Providing an individual who has

tested positive for COVID-19

Administering hydroxychloroquine,

azithromycin, vitamin C, vitamin D,

zinc to the individual on days 1 to 5

Administering hydroxychloroquine,

vitamin C, vitamin D, and zinc to the

individual on days 6 to 10

Monitoring individuals condition over

a pre-determined amount of time

Fig. 3

Providing an individual who has

tested positive for COVID-19

Administering hydroxychloroquine,

azithromycin, vitamin C, vitamin D,

zinc to the individual on days 1 to 5

Administering ivermectin,

doxycycline, vitamin C, vitamin D, and

zinc to the individual on days 6 to 10

Monitoring individuals condition over

a pre-determined amount of time

Fig. 4

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28,000

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Genomic Coordinate

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Fig. 5A

Fig. 5B

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12,000

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4,000

4,000

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24,000

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12,000

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